Therapeutic potential of iron modulating drugs in a mouse model of multiple system atrophy
Neurobiol Dis. 2021 Sep 16:105509. doi: 10.1016/j.nbd.2021.105509. Online ahead of print.ABSTRACTMultiple System Atrophy (MSA) is a rare neurodegenerative synucleinopathy which leads to severe disability followed by death within 6-9 years of symptom onset. There is compelling evidence suggesting that biological trace metals like iron and copper play an important role in synucleinopathies like Parkinson's disease and removing excess brain iron using chelators could slow down the disease progression. In human MSA, there is evidence of increased iron in affected brain regions, but role of iron and therapeutic efficacy of iron...
Source: Neurobiology of Disease - September 19, 2021 Category: Neurology Authors: Jay J Shukla Nadia Stefanova Ashley I Bush Gawain McColl David I Finkelstein Erin J McAllum Source Type: research

Differential involvement of insulin receptor substrate (IRS)-1 and IRS-2 in brain insulin signaling is associated with the effects on amyloid pathology in a mouse model of Alzheimer's disease
Neurobiol Dis. 2021 Sep 16:105510. doi: 10.1016/j.nbd.2021.105510. Online ahead of print.ABSTRACTInsulin signaling has been implicated in the metabolism as well as aging and longevity. Type 2 diabetes mellitus and its core pathology, insulin resistance, has also been implicated in the development of Alzheimer's disease (AD) and amyloid-β deposition in humans. By contrast, genetic ablation of the insulin/IGF-1 signaling (IIS) pathway components, e.g. insulin receptor substrate (IRS)-2, has been documented to suppress amyloid-β accumulation in the brains of transgenic mice overexpressing AD mutant β-amyloid pr...
Source: Neurobiology of Disease - September 19, 2021 Category: Neurology Authors: Toshitaka Ochiai Toshiharu Sano Takeru Nagayama Naoto Kubota Takashi Kadowaki Tomoko Wakabayashi Takeshi Iwatsubo Source Type: research

Second hit hypothesis in dystonia: Dysfunctional cross talk between neuroplasticity and environment?
Neurobiol Dis. 2021 Sep 16;159:105511. doi: 10.1016/j.nbd.2021.105511. Online ahead of print.ABSTRACTOne of the great mysteries in dystonia pathophysiology is the role of environmental factors in disease onset and development. Progress has been made in defining the genetic components of dystonic syndromes, still the mechanisms behind the discrepant relationship between dystonic genotype and phenotype remain largely unclear. Within this review, the preclinical and clinical evidence for environmental stressors as disease modifiers in dystonia pathogenesis are summarized and critically evaluated. The potential role of extrage...
Source: Neurobiology of Disease - September 19, 2021 Category: Neurology Authors: Lisa Rauschenberger Susanne Knorr Antonio Pisani Mark Hallett Jens Volkmann Chi Wang Ip Source Type: research

Alternative platelet activation pathways and their role in neurodegenerative diseases
Neurobiol Dis. 2021 Sep 16;159:105512. doi: 10.1016/j.nbd.2021.105512. Online ahead of print.ABSTRACTPURPOSE OF THE REVIEW: The study of platelets in the context of neurodegenerative diseases is intensifying, and increasing evidence suggests that platelets may play an important role in the pathogenesis of neurodegenerative disorders. Therefore, we aim to provide a comprehensive overview of the role of platelets and their diverse activation pathways in the development of these diseases.RECENT FINDINGS: Platelets participate in synaptic plasticity, learning, memory, and platelets activated by exercise promote neuronal differ...
Source: Neurobiology of Disease - September 19, 2021 Category: Neurology Authors: Paula Ferrer-Ravent ós Katrin Beyer Source Type: research

Therapeutic potential of iron modulating drugs in a mouse model of multiple system atrophy
Neurobiol Dis. 2021 Sep 16:105509. doi: 10.1016/j.nbd.2021.105509. Online ahead of print.ABSTRACTMultiple System Atrophy (MSA) is a rare neurodegenerative synucleinopathy which leads to severe disability followed by death within 6-9 years of symptom onset. There is compelling evidence suggesting that biological trace metals like iron and copper play an important role in synucleinopathies like Parkinson's disease and removing excess brain iron using chelators could slow down the disease progression. In human MSA, there is evidence of increased iron in affected brain regions, but role of iron and therapeutic efficacy of iron...
Source: Neurobiology of Disease - September 19, 2021 Category: Neurology Authors: Jay J Shukla Nadia Stefanova Ashley I Bush Gawain McColl David I Finkelstein Erin J McAllum Source Type: research

Differential involvement of insulin receptor substrate (IRS)-1 and IRS-2 in brain insulin signaling is associated with the effects on amyloid pathology in a mouse model of Alzheimer's disease
Neurobiol Dis. 2021 Sep 16:105510. doi: 10.1016/j.nbd.2021.105510. Online ahead of print.ABSTRACTInsulin signaling has been implicated in the metabolism as well as aging and longevity. Type 2 diabetes mellitus and its core pathology, insulin resistance, has also been implicated in the development of Alzheimer's disease (AD) and amyloid-β deposition in humans. By contrast, genetic ablation of the insulin/IGF-1 signaling (IIS) pathway components, e.g. insulin receptor substrate (IRS)-2, has been documented to suppress amyloid-β accumulation in the brains of transgenic mice overexpressing AD mutant β-amyloid pr...
Source: Neurobiology of Disease - September 19, 2021 Category: Neurology Authors: Toshitaka Ochiai Toshiharu Sano Takeru Nagayama Naoto Kubota Takashi Kadowaki Tomoko Wakabayashi Takeshi Iwatsubo Source Type: research

Second hit hypothesis in dystonia: Dysfunctional cross talk between neuroplasticity and environment?
Neurobiol Dis. 2021 Sep 16:105511. doi: 10.1016/j.nbd.2021.105511. Online ahead of print.ABSTRACTOne of the great mysteries in dystonia pathophysiology is the role of environmental factors in disease onset and development. Progress has been made in defining the genetic components of dystonic syndromes, still the mechanisms behind the discrepant relationship between dystonic genotype and phenotype remain largely unclear. Within this review, the preclinical and clinical evidence for environmental stressors as disease modifiers in dystonia pathogenesis are summarized and critically evaluated. The potential role of extrageneti...
Source: Neurobiology of Disease - September 19, 2021 Category: Neurology Authors: Lisa Rauschenberger Susanne Knorr Antonio Pisani Mark Hallett Jens Volkmann Chi Wang Ip Source Type: research

Alternative platelet activation pathways and their role in neurodegenerative diseases
Neurobiol Dis. 2021 Sep 16:105512. doi: 10.1016/j.nbd.2021.105512. Online ahead of print.ABSTRACTPURPOSE OF THE REVIEW: The study of platelets in the context of neurodegenerative diseases is intensifying, and increasing evidence suggests that platelets may play an important role in the pathogenesis of neurodegenerative disorders. Therefore, we aim to provide a comprehensive overview of the role of platelets and their diverse activation pathways in the development of these diseases.RECENT FINDINGS: Platelets participate in synaptic plasticity, learning, memory, and platelets activated by exercise promote neuronal differenti...
Source: Neurobiology of Disease - September 19, 2021 Category: Neurology Authors: Paula Ferrer-Ravent ós Katrin Beyer Source Type: research

Therapeutic potential of iron modulating drugs in a mouse model of multiple system atrophy
Neurobiol Dis. 2021 Sep 16:105509. doi: 10.1016/j.nbd.2021.105509. Online ahead of print.ABSTRACTMultiple System Atrophy (MSA) is a rare neurodegenerative synucleinopathy which leads to severe disability followed by death within 6-9 years of symptom onset. There is compelling evidence suggesting that biological trace metals like iron and copper play an important role in synucleinopathies like Parkinson's disease and removing excess brain iron using chelators could slow down the disease progression. In human MSA, there is evidence of increased iron in affected brain regions, but role of iron and therapeutic efficacy of iron...
Source: Neurobiology of Disease - September 19, 2021 Category: Neurology Authors: Jay J Shukla Nadia Stefanova Ashley I Bush Gawain McColl David I Finkelstein Erin J McAllum Source Type: research

Differential involvement of insulin receptor substrate (IRS)-1 and IRS-2 in brain insulin signaling is associated with the effects on amyloid pathology in a mouse model of Alzheimer's disease
Neurobiol Dis. 2021 Sep 16:105510. doi: 10.1016/j.nbd.2021.105510. Online ahead of print.ABSTRACTInsulin signaling has been implicated in the metabolism as well as aging and longevity. Type 2 diabetes mellitus and its core pathology, insulin resistance, has also been implicated in the development of Alzheimer's disease (AD) and amyloid-β deposition in humans. By contrast, genetic ablation of the insulin/IGF-1 signaling (IIS) pathway components, e.g. insulin receptor substrate (IRS)-2, has been documented to suppress amyloid-β accumulation in the brains of transgenic mice overexpressing AD mutant β-amyloid pr...
Source: Neurobiology of Disease - September 19, 2021 Category: Neurology Authors: Toshitaka Ochiai Toshiharu Sano Takeru Nagayama Naoto Kubota Takashi Kadowaki Tomoko Wakabayashi Takeshi Iwatsubo Source Type: research

Second hit hypothesis in dystonia: Dysfunctional cross talk between neuroplasticity and environment?
Neurobiol Dis. 2021 Sep 16:105511. doi: 10.1016/j.nbd.2021.105511. Online ahead of print.ABSTRACTOne of the great mysteries in dystonia pathophysiology is the role of environmental factors in disease onset and development. Progress has been made in defining the genetic components of dystonic syndromes, still the mechanisms behind the discrepant relationship between dystonic genotype and phenotype remain largely unclear. Within this review, the preclinical and clinical evidence for environmental stressors as disease modifiers in dystonia pathogenesis are summarized and critically evaluated. The potential role of extrageneti...
Source: Neurobiology of Disease - September 19, 2021 Category: Neurology Authors: Lisa Rauschenberger Susanne Knorr Antonio Pisani Mark Hallett Jens Volkmann Chi Wang Ip Source Type: research

Alternative platelet activation pathways and their role in neurodegenerative diseases
Neurobiol Dis. 2021 Sep 16:105512. doi: 10.1016/j.nbd.2021.105512. Online ahead of print.ABSTRACTPURPOSE OF THE REVIEW: The study of platelets in the context of neurodegenerative diseases is intensifying, and increasing evidence suggests that platelets may play an important role in the pathogenesis of neurodegenerative disorders. Therefore, we aim to provide a comprehensive overview of the role of platelets and their diverse activation pathways in the development of these diseases.RECENT FINDINGS: Platelets participate in synaptic plasticity, learning, memory, and platelets activated by exercise promote neuronal differenti...
Source: Neurobiology of Disease - September 19, 2021 Category: Neurology Authors: Paula Ferrer-Ravent ós Katrin Beyer Source Type: research

Heterozygous GBA D490V and ATP13a2 mutations do not exacerbate pathological α-synuclein spread in the prodromal preformed fibrils model in young mice
Neurobiol Dis. 2021 Sep 15:105513. doi: 10.1016/j.nbd.2021.105513. Online ahead of print.ABSTRACTAutophagic dysregulation and lysosomal impairment have been implicated in the pathogenesis of Parkinson's disease, partly due to the identification of mutations in multiple genes involved in these pathways such as GBA, SNCA, ATP13a2 (also known as PARK9), TMEM175 and LRRK2. Mutations resulting in lysosomal dysfunction are proposed to contribute to Parkinson's disease by increasing α-synuclein levels, that in turn may promote aggregation of this protein. Here, we used two different genetic models-one heterozygous for a mut...
Source: Neurobiology of Disease - September 18, 2021 Category: Neurology Authors: Michaela E Johnson Liza Bergkvist Lucas Stetzik Jennifer A Steiner Lindsay Meyerdirk Emily Schulz Emily Wolfrum Kelvin C Luk Daniel W Wesson Dimitri Krainc Patrik Brundin Source Type: research

Altered cardiac structure and function is related to seizure frequency in a rat model of chronic acquired temporal lobe epilepsy
This study aimed to prospectively examine cardiac structure and function in the kainic acid-induced post-status epilepticus (post-KA SE) model of chronic acquired temporal lobe epilepsy (TLE), specifically to examine for changes between the pre-epileptic, early epileptogenesis and the chronic epilepsy stages. We also aimed to examine whether any changes related to the seizure frequency in individual animals.METHODS: Four hours of SE was induced in 9 male Wistar rats at 10 weeks of age, with 8 saline treated matched control rats. Echocardiography was performed prior to the induction of SE, two- and 10-weeks post-SE. Two wee...
Source: Neurobiology of Disease - September 14, 2021 Category: Neurology Authors: Kim L Powell Zining Liu Claire L Curl Antonia J A Raaijmakers Pragati Sharma Emma L Braine Flavia M Gomes Shobi Sivathamboo Vaughan G Macefield Pablo M Casillas-Espinosa Nigel C Jones Lea M Delbridge Terence J O'Brien Source Type: research

Altered cardiac structure and function is related to seizure frequency in a rat model of chronic acquired temporal lobe epilepsy
This study aimed to prospectively examine cardiac structure and function in the kainic acid-induced post-status epilepticus (post-KA SE) model of chronic acquired temporal lobe epilepsy (TLE), specifically to examine for changes between the pre-epileptic, early epileptogenesis and the chronic epilepsy stages. We also aimed to examine whether any changes related to the seizure frequency in individual animals.METHODS: Four hours of SE was induced in 9 male Wistar rats at 10 weeks of age, with 8 saline treated matched control rats. Echocardiography was performed prior to the induction of SE, two- and 10-weeks post-SE. Two wee...
Source: Neurobiology of Disease - September 14, 2021 Category: Neurology Authors: Kim L Powell Zining Liu Claire L Curl Antonia J A Raaijmakers Pragati Sharma Emma L Braine Flavia M Gomes Shobi Sivathamboo Vaughan G Macefield Pablo M Casillas-Espinosa Nigel C Jones Lea M Delbridge Terence J O'Brien Source Type: research

Altered cardiac structure and function is related to seizure frequency in a rat model of chronic acquired temporal lobe epilepsy
This study aimed to prospectively examine cardiac structure and function in the kainic acid-induced post-status epilepticus (post-KA SE) model of chronic acquired temporal lobe epilepsy (TLE), specifically to examine for changes between the pre-epileptic, early epileptogenesis and the chronic epilepsy stages. We also aimed to examine whether any changes related to the seizure frequency in individual animals.METHODS: Four hours of SE was induced in 9 male Wistar rats at 10 weeks of age, with 8 saline treated matched control rats. Echocardiography was performed prior to the induction of SE, two- and 10-weeks post-SE. Two wee...
Source: Neurobiology of Disease - September 14, 2021 Category: Neurology Authors: Kim L Powell Zining Liu Claire L Curl Antonia J A Raaijmakers Pragati Sharma Emma L Braine Flavia M Gomes Shobi Sivathamboo Vaughan G Macefield Pablo M Casillas-Espinosa Nigel C Jones Lea M Delbridge Terence J O'Brien Source Type: research

Altered cardiac structure and function is related to seizure frequency in a rat model of chronic acquired temporal lobe epilepsy
This study aimed to prospectively examine cardiac structure and function in the kainic acid-induced post-status epilepticus (post-KA SE) model of chronic acquired temporal lobe epilepsy (TLE), specifically to examine for changes between the pre-epileptic, early epileptogenesis and the chronic epilepsy stages. We also aimed to examine whether any changes related to the seizure frequency in individual animals.METHODS: Four hours of SE was induced in 9 male Wistar rats at 10 weeks of age, with 8 saline treated matched control rats. Echocardiography was performed prior to the induction of SE, two- and 10-weeks post-SE. Two wee...
Source: Neurobiology of Disease - September 14, 2021 Category: Neurology Authors: Kim L Powell Zining Liu Claire L Curl Antonia J A Raaijmakers Pragati Sharma Emma L Braine Flavia M Gomes Shobi Sivathamboo Vaughan G Macefield Pablo M Casillas-Espinosa Nigel C Jones Lea M Delbridge Terence J O'Brien Source Type: research

Formalin RT-QuIC assay detects prion-seeding activity in formalin-fixed brain samples from sporadic Creutzfeldt-Jakob disease patients
CONCLUSION: RT-QuIC enables the study of formalin-fixed brain tissue from sCJD patients that has not previously been amenable to analysis.PMID:34509607 | DOI:10.1016/j.nbd.2021.105504 (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - September 12, 2021 Category: Neurology Authors: Thi-Thu-Trang Dong Akio Akagi Toshiaki Nonaka Takehiro Nakagaki Ban Mihara Masaki Takao Yasushi Iwasaki Noriyuki Nishida Katsuya Satoh Source Type: research

A novel glucosylceramide synthase inhibitor attenuates alpha synuclein pathology and lysosomal dysfunction in preclinical models of synucleinopathy
Neurobiol Dis. 2021 Sep 9:105507. doi: 10.1016/j.nbd.2021.105507. Online ahead of print.ABSTRACTMutations in the lysosomal enzyme glucocerebrosidase (GCase, GBA1 gene) are the most common genetic risk factor for developing Parkinson's disease (PD). GCase metabolizes the glycosphingolipids glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph). Mutations in GBA1 reduce enzyme activity and the resulting accumulation of glycosphingolipids may contribute to the underlying pathology of PD, possibly via altering lysosomal function. While reduction of GCase activity exacerbates α-synuclein (α-syn) aggregation, it ...
Source: Neurobiology of Disease - September 12, 2021 Category: Neurology Authors: Mali Cosden Sarah Jinn Lihang Yao Cheryl A Gretzula Monika Kandebo Dawn Toolan Nathan G Hatcher Lei Ma Wei Lemaire Gregory C Adam Christine Burlein Christina Minnick Rose Flick Marla L Watt James Mulhearn Mark Fraley Robert E Drolet Jacob N Marcus Sean M Source Type: research

Obstructive sleep apneas naturally occur in mice during rem sleep and are highly prevalent in a mouse model of down syndrome
CONCLUSIONS: Mice physiologically exhibit both CSAs and OSAs. The latter appear almost exclusively during REMS, and are highly prevalent in Ts65Dn. Mice may, thus, represent a useful model to accelerate the understanding of the pathophysiology and genetics of sleep-disordered breathing and to help the development of new therapies.PMID:34509609 | DOI:10.1016/j.nbd.2021.105508 (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - September 12, 2021 Category: Neurology Authors: Maria Lavinia Bartolucci Chiara Berteotti Sara Alvente Stefano Bastianini Sandra Guidi Viviana Lo Martire Gabriele Matteoli Alessandro Silvani Fiorenza Stagni Marcello Bosi Giulio Alessandri-Bonetti Renata Bartesaghi Giovanna Zoccoli Source Type: research

Formalin RT-QuIC assay detects prion-seeding activity in formalin-fixed brain samples from sporadic Creutzfeldt-Jakob disease patients
CONCLUSION: RT-QuIC enables the study of formalin-fixed brain tissue from sCJD patients that has not previously been amenable to analysis.PMID:34509607 | DOI:10.1016/j.nbd.2021.105504 (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - September 12, 2021 Category: Neurology Authors: Thi-Thu-Trang Dong Akio Akagi Toshiaki Nonaka Takehiro Nakagaki Ban Mihara Masaki Takao Yasushi Iwasaki Noriyuki Nishida Katsuya Satoh Source Type: research

A novel glucosylceramide synthase inhibitor attenuates alpha synuclein pathology and lysosomal dysfunction in preclinical models of synucleinopathy
Neurobiol Dis. 2021 Sep 9:105507. doi: 10.1016/j.nbd.2021.105507. Online ahead of print.ABSTRACTMutations in the lysosomal enzyme glucocerebrosidase (GCase, GBA1 gene) are the most common genetic risk factor for developing Parkinson's disease (PD). GCase metabolizes the glycosphingolipids glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph). Mutations in GBA1 reduce enzyme activity and the resulting accumulation of glycosphingolipids may contribute to the underlying pathology of PD, possibly via altering lysosomal function. While reduction of GCase activity exacerbates α-synuclein (α-syn) aggregation, it ...
Source: Neurobiology of Disease - September 12, 2021 Category: Neurology Authors: Mali Cosden Sarah Jinn Lihang Yao Cheryl A Gretzula Monika Kandebo Dawn Toolan Nathan G Hatcher Lei Ma Wei Lemaire Gregory C Adam Christine Burlein Christina Minnick Rose Flick Marla L Watt James Mulhearn Mark Fraley Robert E Drolet Jacob N Marcus Sean M Source Type: research

Obstructive sleep apneas naturally occur in mice during rem sleep and are highly prevalent in a mouse model of down syndrome
CONCLUSIONS: Mice physiologically exhibit both CSAs and OSAs. The latter appear almost exclusively during REMS, and are highly prevalent in Ts65Dn. Mice may, thus, represent a useful model to accelerate the understanding of the pathophysiology and genetics of sleep-disordered breathing and to help the development of new therapies.PMID:34509609 | DOI:10.1016/j.nbd.2021.105508 (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - September 12, 2021 Category: Neurology Authors: Maria Lavinia Bartolucci Chiara Berteotti Sara Alvente Stefano Bastianini Sandra Guidi Viviana Lo Martire Gabriele Matteoli Alessandro Silvani Fiorenza Stagni Marcello Bosi Giulio Alessandri-Bonetti Renata Bartesaghi Giovanna Zoccoli Source Type: research

Formalin RT-QuIC assay detects prion-seeding activity in formalin-fixed brain samples from sporadic Creutzfeldt-Jakob disease patients
CONCLUSION: RT-QuIC enables the study of formalin-fixed brain tissue from sCJD patients that has not previously been amenable to analysis.PMID:34509607 | DOI:10.1016/j.nbd.2021.105504 (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - September 12, 2021 Category: Neurology Authors: Thi-Thu-Trang Dong Akio Akagi Toshiaki Nonaka Takehiro Nakagaki Ban Mihara Masaki Takao Yasushi Iwasaki Noriyuki Nishida Katsuya Satoh Source Type: research

A novel glucosylceramide synthase inhibitor attenuates alpha synuclein pathology and lysosomal dysfunction in preclinical models of synucleinopathy
Neurobiol Dis. 2021 Sep 9:105507. doi: 10.1016/j.nbd.2021.105507. Online ahead of print.ABSTRACTMutations in the lysosomal enzyme glucocerebrosidase (GCase, GBA1 gene) are the most common genetic risk factor for developing Parkinson's disease (PD). GCase metabolizes the glycosphingolipids glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph). Mutations in GBA1 reduce enzyme activity and the resulting accumulation of glycosphingolipids may contribute to the underlying pathology of PD, possibly via altering lysosomal function. While reduction of GCase activity exacerbates α-synuclein (α-syn) aggregation, it ...
Source: Neurobiology of Disease - September 12, 2021 Category: Neurology Authors: Mali Cosden Sarah Jinn Lihang Yao Cheryl A Gretzula Monika Kandebo Dawn Toolan Nathan G Hatcher Lei Ma Wei Lemaire Gregory C Adam Christine Burlein Christina Minnick Rose Flick Marla L Watt James Mulhearn Mark Fraley Robert E Drolet Jacob N Marcus Sean M Source Type: research

Obstructive sleep apneas naturally occur in mice during rem sleep and are highly prevalent in a mouse model of down syndrome
CONCLUSIONS: Mice physiologically exhibit both CSAs and OSAs. The latter appear almost exclusively during REMS, and are highly prevalent in Ts65Dn. Mice may, thus, represent a useful model to accelerate the understanding of the pathophysiology and genetics of sleep-disordered breathing and to help the development of new therapies.PMID:34509609 | DOI:10.1016/j.nbd.2021.105508 (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - September 12, 2021 Category: Neurology Authors: Maria Lavinia Bartolucci Chiara Berteotti Sara Alvente Stefano Bastianini Sandra Guidi Viviana Lo Martire Gabriele Matteoli Alessandro Silvani Fiorenza Stagni Marcello Bosi Giulio Alessandri-Bonetti Renata Bartesaghi Giovanna Zoccoli Source Type: research

High-fat diet alters stress behavior, inflammatory parameters and gut microbiota in Tg APP mice in a sex-specific manner
In this study, we have analyzed the effects of a prolonged (18 weeks, starting at 7 months of age) HFD on male and female mice, both wild type (WT) and TgAPP mice, a model for AD, investigating the behavioral profile, gut microbiota composition and inflammatory/phagocytosis-related gene expression in hippocampus. In the open-field test, no overt differences in motor activity were observed between male and female or WT and TgAPP mice on a low-fat diet (LFD). However, HFD induced anxiety, as judged by decreased motor activity and increased time in the margins in the open-field, and a trend towards increased immobility time i...
Source: Neurobiology of Disease - September 3, 2021 Category: Neurology Authors: Natalia Yanguas-Cas ás Cristina Torres Andrea Crespo-Castrillo Sonia Diaz-Pacheco Kiera Healy Catherine Stanton Julie A Chowen Luis M Garcia-Segura Maria Angeles Arevalo John F Cryan Maria L de Ceballos Source Type: research

Elezanumab, a clinical stage human monoclonal antibody that selectively targets repulsive guidance molecule A to promote neuroregeneration and neuroprotection in neuronal injury and demyelination models
Neurobiol Dis. 2021 Aug 31;159:105492. doi: 10.1016/j.nbd.2021.105492. Online ahead of print.ABSTRACTRepulsive guidance molecule A (RGMa) is a potent inhibitor of axonal growth and a regulator of neuronal cell death. It is up-regulated following neuronal injury and accumulates in chronic neurodegenerative diseases. Neutralizing RGMa has the potential to promote neuroregeneration and neuroprotection. Previously we reported that a rat anti-N terminal RGMa (N-RGMa) antibody r5F9 and its humanized version h5F9 (ABT-207) promote neuroprotection and neuroregeneration in preclinical neurodegenerative disease models. However, due ...
Source: Neurobiology of Disease - September 3, 2021 Category: Neurology Authors: Lili Huang Emma Fung Sahana Bose Andreas Popp Preethne B öser John Memmott Yuliya A Kutskova Renee Miller Edit Tarcsa Corinna Klein Geertruida M Veldman Bernhard K Mueller Yi-Fang Cui Source Type: research

High-fat diet alters stress behavior, inflammatory parameters and gut microbiota in Tg APP mice in a sex-specific manner
In this study, we have analyzed the effects of a prolonged (18 weeks, starting at 7 months of age) HFD on male and female mice, both wild type (WT) and TgAPP mice, a model for AD, investigating the behavioral profile, gut microbiota composition and inflammatory/phagocytosis-related gene expression in hippocampus. In the open-field test, no overt differences in motor activity were observed between male and female or WT and TgAPP mice on a low-fat diet (LFD). However, HFD induced anxiety, as judged by decreased motor activity and increased time in the margins in the open-field, and a trend towards increased immobility time i...
Source: Neurobiology of Disease - September 3, 2021 Category: Neurology Authors: Natalia Yanguas-Cas ás Cristina Torres Andrea Crespo-Castrillo Sonia Diaz-Pacheco Kiera Healy Catherine Stanton Julie A Chowen Luis M Garcia-Segura Maria Angeles Arevalo John F Cryan Maria L de Ceballos Source Type: research

Elezanumab, a clinical stage human monoclonal antibody that selectively targets repulsive guidance molecule A to promote neuroregeneration and neuroprotection in neuronal injury and demyelination models
Neurobiol Dis. 2021 Aug 31;159:105492. doi: 10.1016/j.nbd.2021.105492. Online ahead of print.ABSTRACTRepulsive guidance molecule A (RGMa) is a potent inhibitor of axonal growth and a regulator of neuronal cell death. It is up-regulated following neuronal injury and accumulates in chronic neurodegenerative diseases. Neutralizing RGMa has the potential to promote neuroregeneration and neuroprotection. Previously we reported that a rat anti-N terminal RGMa (N-RGMa) antibody r5F9 and its humanized version h5F9 (ABT-207) promote neuroprotection and neuroregeneration in preclinical neurodegenerative disease models. However, due ...
Source: Neurobiology of Disease - September 3, 2021 Category: Neurology Authors: Lili Huang Emma Fung Sahana Bose Andreas Popp Preethne B öser John Memmott Yuliya A Kutskova Renee Miller Edit Tarcsa Corinna Klein Geertruida M Veldman Bernhard K Mueller Yi-Fang Cui Source Type: research

High-fat diet alters stress behavior, inflammatory parameters and gut microbiota in Tg APP mice in a sex-specific manner
In this study, we have analyzed the effects of a prolonged (18 weeks, starting at 7 months of age) HFD on male and female mice, both wild type (WT) and TgAPP mice, a model for AD, investigating the behavioral profile, gut microbiota composition and inflammatory/phagocytosis related gene expression in hippocampus. In the open-field test, no overt differences in motor activity were observed between male and female or WT and TgAPP mice on a low-fat diet (LFD). However, HFD induced anxiety, as judged by decreased motor activity and increased time in the margins in the open-field, and a trend towards increased immobility time i...
Source: Neurobiology of Disease - September 3, 2021 Category: Neurology Authors: Natalia Yanguas-Cas ás Cristina Torres Andrea Crespo-Castrillo Sonia Diaz-Pacheco Kiera Healy Catherine Stanton Julie A Chowen Luis M Garcia-Segura Mar ía Ángeles Arévalo John F Cryan Maria L de Ceballos Source Type: research

Elezanumab, a clinical stage human monoclonal antibody that selectively targets repulsive guidance molecule A to promote neuroregeneration and neuroprotection in neuronal injury and demyelination models
Neurobiol Dis. 2021 Aug 31;159:105492. doi: 10.1016/j.nbd.2021.105492. Online ahead of print.ABSTRACTRepulsive guidance molecule A (RGMa) is a potent inhibitor of axonal growth and a regulator of neuronal cell death. It is up-regulated following neuronal injury and accumulates in chronic neurodegenerative diseases. Neutralizing RGMa has the potential to promote neuroregeneration and neuroprotection. Previously we reported that a rat anti-N terminal RGMa (N-RGMa) antibody r5F9 and its humanized version h5F9 (ABT-207) promote neuroprotection and neuroregeneration in preclinical neurodegenerative disease models. However, due ...
Source: Neurobiology of Disease - September 3, 2021 Category: Neurology Authors: Lili Huang Emma Fung Sahana Bose Andreas Popp Preethne B öser John Memmott Yuliya A Kutskova Renee Miller Edit Tarcsa Corinna Klein Geertruida M Veldman Bernhard K Mueller Yi-Fang Cui Source Type: research

Amyloid beta acts synergistically as a pro-inflammatory cytokine
Neurobiol Dis. 2021 Aug 28:105493. doi: 10.1016/j.nbd.2021.105493. Online ahead of print.ABSTRACTThe amyloid beta (Aβ) peptide is believed to play a central role in Alzheimer's disease (AD), the most common age-related neurodegenerative disorder. However, the natural, evolutionarily selected functions of Aβ are incompletely understood. Here, we report that nanomolar concentrations of Aβ act synergistically with known cytokines to promote pro-inflammatory activation in primary human astrocytes (a cell type increasingly implicated in brain aging and AD). Using transcriptomics (RNA-seq), we show that Aβ ca...
Source: Neurobiology of Disease - August 31, 2021 Category: Neurology Authors: Thomas J LaRocca Alyssa N Cavalier Christine M Roberts Maddie R Lemieux Pooja Ramesh Micklaus A Garcia Christopher D Link Source Type: research

Genetic ablation of Gpnmb does not alter synuclein-related pathology
Neurobiol Dis. 2021 Aug 28:105494. doi: 10.1016/j.nbd.2021.105494. Online ahead of print.ABSTRACTThe gene GPNMB is known to play roles in phagocytosis and tissue repair, and is upregulated in microglia in many mouse models of neurodegenerative disease as well as in human patients. Nearby genomic variants are associated with both elevated Parkinson's disease (PD) risk and higher expression of this gene, suggesting that inhibiting GPNMB activity might be protective in Parkinson's disease. We tested this hypothesis in three different mouse models of neurological diseases: a remyelination model and two models of alpha-synuclei...
Source: Neurobiology of Disease - August 31, 2021 Category: Neurology Authors: Robert Brendza Han Lin Kimberly Stark Oded Foreman Janet Tao Andrew Pierce Hai Ngu Kimberle Shen Amy E Easton Tushar Bhangale Diana Chang Baris Bingol Brad A Friedman Source Type: research

The cross-hemispheric nigrostriatal pathway prevents the expression of levodopa-induced dyskinesias
Neurobiol Dis. 2021 Aug 27;159:105491. doi: 10.1016/j.nbd.2021.105491. Online ahead of print.ABSTRACTParkinson's disease (PD) is a neurodegenerative movement disorder that is routinely treated with levodopa. Unfortunately, long-term dopamine replacement therapy using levodopa leads to levodopa-induced dyskinesias (LID), a significant and disabling side-effect. Clinical findings indicate that LID typically only occurs following the progression of PD motor symptoms from the unilateral (Hoehn and Yahr (HY) Stage I) to the bilateral stage (HY Stage II). This suggests the presence of some compensatory interhemispheric mechanism...
Source: Neurobiology of Disease - August 30, 2021 Category: Neurology Authors: Vishakh Iyer Kala Venkiteswaran Sandip Savaliya Christopher A Lieu Erin Handly Timothy P Gilmour Allen R Kunselman Thyagarajan Subramanian Source Type: research

Valproic acid suppresses cuprizone-induced hippocampal demyelination and anxiety-like behavior by promoting cholesterol biosynthesis
Neurobiol Dis. 2021 Aug 27;158:105489. doi: 10.1016/j.nbd.2021.105489. Online ahead of print.ABSTRACTMyelin consists of several layers of tightly compacted membranes that form an insulating sheath around axons. These membranes are highly enriched in cholesterol, which is essential for the myelination process. Proper myelination is crucial for various neurophysiological functions while demyelination may cause CNS disease, such as multiple sclerosis (MS). Recent studies demonstrated that demyelination occurs not only in the white matter but also in the grey matter, such as the hippocampus, which may cause cognitive deficits ...
Source: Neurobiology of Disease - August 30, 2021 Category: Neurology Authors: Xinjian Zhu Yuanyuan Yao Yang Hu Jiurong Yang Canyu Zhang Yuqi He Aifeng Zhang Xiufang Liu Chenchen Zhang Guangming Gan Source Type: research

Neurophysiological responses of globus pallidus internus during the auditory oddball task in Parkinson's disease
Neurobiol Dis. 2021 Aug 27;159:105490. doi: 10.1016/j.nbd.2021.105490. Online ahead of print.ABSTRACTParkinson's disease can be associated with significant cognitive impairment that may lead to dementia. Deep brain stimulation (DBS) of the subthalamic nucleus is an effective therapy for motor symptoms but is associated with cognitive decline. DBS of globus pallidus internus (GPi) poses less risk of cognitive decline so may be the preferred target. A research priority is to identify biomarkers of cognitive decline in this population, but efforts are hampered by a lack of understanding of the role of the different basal gang...
Source: Neurobiology of Disease - August 30, 2021 Category: Neurology Authors: Frhan I Alanazi Tameem M Al-Ozzi Suneil K Kalia Mojgan Hodaie Andres M Lozano Melanie Cohn William D Hutchison Source Type: research

The cross-hemispheric nigrostriatal pathway prevents the expression of levodopa-induced dyskinesias
Neurobiol Dis. 2021 Aug 27:105491. doi: 10.1016/j.nbd.2021.105491. Online ahead of print.ABSTRACTParkinson's disease (PD) is a neurodegenerative movement disorder that is routinely treated with levodopa. Unfortunately, long-term dopamine replacement therapy using levodopa leads to levodopa-induced dyskinesias (LID), a significant and disabling side-effect. Clinical findings indicate that LID typically only occurs following the progression of PD motor symptoms from the unilateral (Hoehn and Yahr (HY) Stage I) to the bilateral stage (HY Stage II). This suggests the presence of some compensatory interhemispheric mechanisms th...
Source: Neurobiology of Disease - August 30, 2021 Category: Neurology Authors: Vishakh Iyer Kala Venkiteswaran Sandip Savaliya Christopher A Lieu Erin Handly Timothy P Gilmour Allen R Kunselman Thyagarajan Subramanian Source Type: research

Valproic acid suppresses cuprizone-induced hippocampal demyelination and anxiety-like behavior by promoting cholesterol biosynthesis
Neurobiol Dis. 2021 Aug 27:105489. doi: 10.1016/j.nbd.2021.105489. Online ahead of print.ABSTRACTMyelin consists of several layers of tightly compacted membranes that form an insulating sheath around axons. These membranes are highly enriched in cholesterol, which is essential for the myelination process. Proper myelination is crucial for various neurophysiological functions while demyelination may cause CNS disease, such as multiple sclerosis (MS). Recent studies demonstrated that demyelination occurs not only in the white matter but also in the grey matter, such as the hippocampus, which may cause cognitive deficits and ...
Source: Neurobiology of Disease - August 30, 2021 Category: Neurology Authors: Xinjian Zhu Yuanyuan Yao Yang Hu Jiurong Yang Canyu Zhang Yuqi He Aifeng Zhang Xiufang Liu Chenchen Zhang Guangming Gan Source Type: research

Neurophysiological responses of globus pallidus internus during the auditory oddball task in Parkinson's disease
Neurobiol Dis. 2021 Aug 27:105490. doi: 10.1016/j.nbd.2021.105490. Online ahead of print.ABSTRACTParkinson's disease can be associated with significant cognitive impairment that may lead to dementia. Deep brain stimulation (DBS) of the subthalamic nucleus is an effective therapy for motor symptoms but is associated with cognitive decline. DBS of globus pallidus internus (GPi) poses less risk of cognitive decline so may be the preferred target. A research priority is to identify biomarkers of cognitive decline in this population, but efforts are hampered by a lack of understanding of the role of the different basal ganglia ...
Source: Neurobiology of Disease - August 30, 2021 Category: Neurology Authors: Frhan I Alanazi Tameem Al-Ozzi Suneil K Kalia Mojgan Hodaie Andres M Lozano Melanie Cohn William D Hutchison Source Type: research

Altered synaptic glutamate homeostasis contributes to cognitive decline in young APP/PSEN1 mice
Neurobiol Dis. 2021 Aug 24:105486. doi: 10.1016/j.nbd.2021.105486. Online ahead of print.ABSTRACTNon-convulsive epileptiform activity is a common and under-studied comorbidity of Alzheimer's disease that may significantly contribute to onset of clinical symptoms independently of other neuropathological features such as β-amyloid deposition. We used repeated treatment with low dose kainic acid (KA) to trigger sub-threshold epileptiform activity in young (less than 6 months) wild-type (WT) and APP/PSEN1 to test the role of disruption to the glutamatergic system in epileptiform activity changes and the development of mem...
Source: Neurobiology of Disease - August 27, 2021 Category: Neurology Authors: J M Wilcox D C Consoli A A Tienda S Dixit R A Buchanan J M May W P Nobis F E Harrison Source Type: research

Altered synaptic glutamate homeostasis contributes to cognitive decline in young APP/PSEN1 mice
Neurobiol Dis. 2021 Aug 24:105486. doi: 10.1016/j.nbd.2021.105486. Online ahead of print.ABSTRACTNon-convulsive epileptiform activity is a common and under-studied comorbidity of Alzheimer's disease that may significantly contribute to onset of clinical symptoms independently of other neuropathological features such as β-amyloid deposition. We used repeated treatment with low dose kainic acid (KA) to trigger sub-threshold epileptiform activity in young (less than 6 months) wild-type (WT) and APP/PSEN1 to test the role of disruption to the glutamatergic system in epileptiform activity changes and the development of mem...
Source: Neurobiology of Disease - August 27, 2021 Category: Neurology Authors: J M Wilcox D C Consoli A A Tienda S Dixit R A Buchanan J M May W P Nobis F E Harrison Source Type: research

Altered synaptic glutamate homeostasis contributes to cognitive decline in young APP/PSEN1 mice
Neurobiol Dis. 2021 Aug 24:105486. doi: 10.1016/j.nbd.2021.105486. Online ahead of print.ABSTRACTNon-convulsive epileptiform activity is a common and under-studied comorbidity of Alzheimer's disease that may significantly contribute to onset of clinical symptoms independently of other neuropathological features such as β-amyloid deposition. We used repeated treatment with low dose kainic acid (KA) to trigger sub-threshold epileptiform activity in young (less than 6 months) wild-type (WT) and APP/PSEN1 to test the role of disruption to the glutamatergic system in epileptiform activity changes and the development of mem...
Source: Neurobiology of Disease - August 27, 2021 Category: Neurology Authors: J M Wilcox D C Consoli A A Tienda S Dixit R A Buchanan J M May W P Nobis F E Harrison Source Type: research

Dual SMN inducing therapies can rescue survival and motor unit function in symptomatic ∆7SMA mice
Neurobiol Dis. 2021 Aug 20;159:105488. doi: 10.1016/j.nbd.2021.105488. Online ahead of print.ABSTRACTSpinal muscular atrophy (SMA) is an autosomal recessive disease characterized by survival motor neuron (SMN) protein deficiency which results in motor neuron loss and muscle atrophy. SMA is caused by a mutation or deletion of the survival motor neuron 1 (SMN1) gene and retention of the nearly identical SMN2 gene. SMN2 contains a C to T change in exon 7 that results in exon 7 exclusion from 90% of transcripts. SMN protein lacking exon 7 is unstable and rapidly degraded. The remaining full-length transcripts from SMN2 are ins...
Source: Neurobiology of Disease - August 23, 2021 Category: Neurology Authors: Kaitlyn M Kray Vicki L McGovern Deepti Chugh W David Arnold Arthur H M Burghes Source Type: research

Dual SMN inducing therapies can rescue survival and motor unit function in symptomatic ∆7SMA mice
Neurobiol Dis. 2021 Aug 20;159:105488. doi: 10.1016/j.nbd.2021.105488. Online ahead of print.ABSTRACTSpinal muscular atrophy (SMA) is an autosomal recessive disease characterized by survival motor neuron (SMN) protein deficiency which results in motor neuron loss and muscle atrophy. SMA is caused by a mutation or deletion of the survival motor neuron 1 (SMN1) gene and retention of the nearly identical SMN2 gene. SMN2 contains a C to T change in exon 7 that results in exon 7 exclusion from 90% of transcripts. SMN protein lacking exon 7 is unstable and rapidly degraded. The remaining full-length transcripts from SMN2 are ins...
Source: Neurobiology of Disease - August 23, 2021 Category: Neurology Authors: Kaitlyn M Kray Vicki L McGovern Deepti Chugh W David Arnold Arthur H M Burghes Source Type: research

Dual SMN inducing therapies can rescue survival and motor unit function in symptomatic ∆7SMA mice
Neurobiol Dis. 2021 Aug 20:105488. doi: 10.1016/j.nbd.2021.105488. Online ahead of print.ABSTRACTSpinal muscular atrophy (SMA) is an autosomal recessive disease characterized by survival motor neuron (SMN) protein deficiency which results in motor neuron loss and muscle atrophy. SMA is caused by a mutation or deletion of the survival motor neuron 1 (SMN1) gene and retention of the nearly identical SMN2 gene. SMN2 contains a C to T change in exon 7 that results in exon 7 exclusion from 90% of transcripts. SMN protein lacking exon 7 is unstable and rapidly degraded. The remaining full-length transcripts from SMN2 are insuffi...
Source: Neurobiology of Disease - August 23, 2021 Category: Neurology Authors: Kaitlyn M Kray Vicki L McGovern Deepti Chugh W David Arnold Arthur H M Burghes Source Type: research

Dual SMN inducing therapies can rescue survival and motor unit function in symptomatic ∆7SMA mice
Neurobiol Dis. 2021 Aug 20:105488. doi: 10.1016/j.nbd.2021.105488. Online ahead of print.ABSTRACTSpinal muscular atrophy (SMA) is an autosomal recessive disease characterized by survival motor neuron (SMN) protein deficiency which results in motor neuron loss and muscle atrophy. SMA is caused by a mutation or deletion of the survival motor neuron 1 (SMN1) gene and retention of the nearly identical SMN2 gene. SMN2 contains a C to T change in exon 7 that results in exon 7 exclusion from 90% of transcripts. SMN protein lacking exon 7 is unstable and rapidly degraded. The remaining full-length transcripts from SMN2 are insuffi...
Source: Neurobiology of Disease - August 23, 2021 Category: Neurology Authors: Kaitlyn M Kray Vicki L McGovern Deepti Chugh W David Arnold Arthur H M Burghes Source Type: research

Constitutive silencing of LRRK2 kinase activity leads to early glucocerebrosidase deregulation and late impairment of autophagy in vivo
Neurobiol Dis. 2021 Aug 19:105487. doi: 10.1016/j.nbd.2021.105487. Online ahead of print.ABSTRACTMutations in leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease. LRRK2 modulates the autophagy-lysosome pathway (ALP), a clearance process subserving the quality control of cellular proteins and organelles. Since dysfunctional ALP might lead to α-synuclein accumulation and, hence, Parkinson's disease, LRRK2 kinase modulation of ALP, its age-dependence and relation with pSer129 α-synuclein inclusions were investigated in vivo. Striatal ALP markers were analyzed by Western blotting in 3, 12 a...
Source: Neurobiology of Disease - August 22, 2021 Category: Neurology Authors: Federica Albanese Daniela Mercatelli Luca Finetti Giulia Lamonaca Sara Pizzi Derya R Shimshek Giovanni Bernacchia Michele Morari Source Type: research

Corrigendum to "Long-term seizure dynamics are determined by the nature of seizures and the mutual interactions between them" [Neurobiol. Dis., Volume 154 (2021), Article 105,347]
Neurobiol Dis. 2021 Aug 18:105484. doi: 10.1016/j.nbd.2021.105484. Online ahead of print.NO ABSTRACTPMID:34418569 | DOI:10.1016/j.nbd.2021.105484 (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - August 21, 2021 Category: Neurology Authors: Jan Kudlacek Jan Chvojka Vojtech Kumpost Barbora Hermanovska Antonin Posusta John G R Jefferys Matias I Maturana Ondrej Novak Mark J Cook Jakub Otahal Jaroslav Hlinka Premysl Jiruska Source Type: research

Corrigendum to "Long-term seizure dynamics are determined by the nature of seizures and the mutual interactions between them" [Neurobiol. Dis., Volume 154 (2021), Article 105,347]
Neurobiol Dis. 2021 Aug 18:105484. doi: 10.1016/j.nbd.2021.105484. Online ahead of print.NO ABSTRACTPMID:34418569 | DOI:10.1016/j.nbd.2021.105484 (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - August 21, 2021 Category: Neurology Authors: Jan Kudlacek Jan Chvojka Vojtech Kumpost Barbora Hermanovska Antonin Posusta John G R Jefferys Matias I Maturana Ondrej Novak Mark J Cook Jakub Otahal Jaroslav Hlinka Premysl Jiruska Source Type: research