Intracranial atherosclerotic disease.
Abstract Intracranial atherosclerosis (ICAS) is a progressive pathological process that causes progressive stenosis and cerebral hypoperfusion and is a major cause of stroke occurrence and recurrence around the world. Multiple factors contribute to the development of ICAS. Angiography imaging techniques can improve the diagnosis of and the selection of appropriate treatment regimens for ICAS. Neither aggressive medication nor endovascular interventions can eradicate stroke recurrence in patients with ICAS. Non-pharmacological therapies such as remote ischemic conditioning and hypothermia are emerging. Comprehensiv...
Source: Neurobiology of Disease - November 12, 2018 Category: Neurology Authors: Wang Y, Meng R, Liu G, Cao C, Chen F, Jin K, Ji X, Cao G Tags: Neurobiol Dis Source Type: research

Cognitive functions associated with developing prefrontal cortex during adolescence and developmental neuropsychiatric disorders.
Abstract Cognitive functions including social cognition improve significantly during adolescence, the time period during which the brain typically handles a large volume of incoming information from the outside environment. Processing information and responding to environmental challenges allow the prefrontal cortex, a brain region important for cognition, to mature further and establish self-identity, social skills, and other cognitive abilities, thus helping individuals to function in society. People with vulnerable circuitries predisposed by either genetic or early environmental insults, may not be able to deal...
Source: Neurobiology of Disease - November 10, 2018 Category: Neurology Authors: Sakurai T, Gamo NJ Tags: Neurobiol Dis Source Type: research

Mitochondrial dysfunction in preclinical genetic prion disease: A target for preventive treatment?
Abstract Mitochondrial malfunction is a common feature in advanced stages of neurodegenerative conditions, as is the case for the accumulation of aberrantly folded proteins, such as PrP in prion diseases. In this work, we investigated mitochondrial activity and expression of related factors vis a vis PrP accumulation at the subclinical stages of TgMHu2ME199K mice, modeling for genetic prion diseases. While these mice remain healthy until 5-6 months of age, they succumb to fatal disease at 12-14 months. We found that mitochondrial respiratory chain enzymatic activates and ATP/ROS production, were abnormally ele...
Source: Neurobiology of Disease - November 10, 2018 Category: Neurology Authors: Keller G, Binyamin O, Frid K, Saada A, Gabizon R Tags: Neurobiol Dis Source Type: research

Microsomal prostaglandin E synthase-1 is a critical factor in dopaminergic neurodegeneration in Parkinson's disease.
Abstract Parkinson's disease (PD) is a neurodegenerative disorder of uncertain pathogenesis characterized by the loss of nigrostriatal dopaminergic neurons. Although increased production of prostaglandin E2 (PGE2) has been implicated in tissue damage in several pathological settings, the role of microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal enzyme for PGE2 synthesis, in dopaminergic neurodegeneration remains unclear. Here we show that mPGES-1 is up-regulated in the dopaminergic neurons of the substantia nigra of postmortem brain tissue from PD patients and in neurotoxin 6-hydroxydopamine (...
Source: Neurobiology of Disease - November 10, 2018 Category: Neurology Authors: Ikeda-Matsuo Y, Miyata H, Mizoguchi T, Ohama E, Naito Y, Uematsu S, Akira S, Sasaki Y, Tanabe M Tags: Neurobiol Dis Source Type: research

Calpain activation following spontaneous seizures during early epileptogenesis.
ez MI Abstract Epilepsy is a brain disorder characterized by a predisposition to suffer epileptic seizures. Acquired epilepsy might be the result of brain insults like head trauma, stroke, brain infection, or status epilepticus (SE) when one of these triggering injuries starts a transformative process known as epileptogenesis. There is some data to suggest that, during epileptogenesis, seizures themselves damage the brain but there is no conclusive evidence to demonstrate that spontaneous recurrent seizures themselves injure the brain. Our recent evidence indicates calpain overactivation might be relevant for epil...
Source: Neurobiology of Disease - November 10, 2018 Category: Neurology Authors: Lam PM, González MI Tags: Neurobiol Dis Source Type: research

Deep brain stimulation of the pedunculopontine nucleus modulates subthalamic pathological oscillations.
Abstract Low frequency deep brain stimulation (DBS) of the pedunculopontine nucleus area (PPNa) has been proposed as a novel surgical target for gait dysfunction in the late stage of Parkinson's disease (PD). Since the mid-2000s, we have shown that intrasurgical delivery of stimulation in the pontine tegmentum affects the firing activity in the subthalamic nucleus (STN), but its effect on STN oscillatory rhythms has not been studied. Neuronal oscillations detected by local field potential (LFPs) have great importance, since they express complex movement-related behavior such as locomotion. Therefore, we examined t...
Source: Neurobiology of Disease - November 10, 2018 Category: Neurology Authors: Stefani A, Grandi LC, Galati S Tags: Neurobiol Dis Source Type: research

Astrocytic expression of the chaperone DNAJB6 results in non-cell autonomous protection in Huntington's disease.
Abstract Several neurodegenerative diseases like Huntington's, a polyglutamine (PolyQ) disease, are initiated by protein aggregation in neurons. Furthermore, these diseases are also associated with a multitude of responses in non-neuronal cells in the brain, in particular glial cells, like astrocytes. These non-neuronal responses have repeatedly been suggested to play a disease-modulating role, but how these may be exploited to delay the progression of neurodegeneration has remained unclear. Interestingly, one of the molecular changes that astrocytes undergo includes the upregulation of certain Heat Shock Proteins...
Source: Neurobiology of Disease - November 5, 2018 Category: Neurology Authors: Bason M, Meister-Broekema M, Alberts N, Dijkers P, Bergink S, Sibon OCM, Kampinga HH Tags: Neurobiol Dis Source Type: research

Portrait of blood-derived extracellular vesicles in patients with Parkinson's disease.
tti F Abstract The production of extracellular vesicles (EV) is a ubiquitous feature of eukaryotic cells but pathological events can affect their formation and constituents. We sought to characterize the nature, profile and protein signature of EV in the plasma of Parkinson's disease (PD) patients and how they correlate to clinical measures of the disease. EVs were initially collected from cohorts of PD (n = 60; Controls, n = 37) and Huntington's disease (HD) patients (Pre-manifest, n = 11; manifest, n = 52; Controls, n = 55) - for comparative purposes in individuals with another chronic neurod...
Source: Neurobiology of Disease - November 5, 2018 Category: Neurology Authors: Lamontagne-Proulx J, St-Amour I, Labib R, Pilon J, Denis HL, Cloutier N, Roux-Dalvai F, Vincent AT, Mason SL, Duchez AC, Droit A, Lacroix S, Dupré N, Langlois M, Chouinard S, Panisset M, Barker RA, Boilard E, Cicchetti F Tags: Neurobiol Dis Source Type: research

Dopaminergic degeneration induces early posterior cortical thinning in Parkinson's disease.
DISCUSSION: To date, posterior cortical alterations in PD, known to play a major role in the development of PD-dementia, have mainly been attributed to a cholinergic degeneration occurring in later stages of the disease. Our results suggest that dopamine loss also promotes posterior-cortical atrophy from the very early stages of Parkinson's disease, which may have potential clinical and therapeutic implications. PMID: 30408592 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - November 5, 2018 Category: Neurology Authors: Sampedro F, Marín-Lahoz J, Martínez-Horta S, Pagonabarraga J, Kulisevsky J Tags: Neurobiol Dis Source Type: research

Deceleration of the neurodegenerative phenotype in pyroglutamate-A β accumulating transgenic mice by oral treatment with the Aβ oligomer eliminating compound RD2.
Deceleration of the neurodegenerative phenotype in pyroglutamate-Aβ accumulating transgenic mice by oral treatment with the Aβ oligomer eliminating compound RD2. Neurobiol Dis. 2018 Nov 01;: Authors: Schemmert S, Schartmann E, Honold D, Zafiu C, Ziehm T, Langen KJ, Shah NJ, Kutzsche J, Willuweit A, Willbold D Abstract Alzheimer's disease, a multifactorial incurable disorder, is mainly characterised by progressive neurodegeneration, extracellular accumulation of amyloid-β protein (Aβ), and intracellular aggregation of hyperphosphorylated tau protein. During the last years, Aβ o...
Source: Neurobiology of Disease - November 1, 2018 Category: Neurology Authors: Schemmert S, Schartmann E, Honold D, Zafiu C, Ziehm T, Langen KJ, Shah NJ, Kutzsche J, Willuweit A, Willbold D Tags: Neurobiol Dis Source Type: research

Modulation of inhibitory plasticity in basal ganglia output nuclei of patients with Parkinson's disease.
Abstract Deep brain stimulation of certain target structures within the basal ganglia is an effective therapy for the management of the motor symptoms of Parkinson's disease. However, its mechanisms, as well as the pathophysiology of Parkinson's disease, are varied and complex. The classical model of Parkinson's disease states that symptoms may arise as a result of increased neuronal activity in the basal ganglia output nuclei due to downregulated GABAergic striato-nigral/-pallidal projections. We sought to investigate the stimulation and levodopa induced effects on inhibitory synaptic plasticity in these basal ga...
Source: Neurobiology of Disease - November 1, 2018 Category: Neurology Authors: Milosevic L, Gramer R, Kim TH, Algarni M, Fasano A, Kalia SK, Hodaie M, Lozano AM, Popovic MR, Hutchison WD Tags: Neurobiol Dis Source Type: research

Neurobiology and treatment of social cognition in schizophrenia: Bridging the bed-bench gap.
Abstract Social cognition refers to the psychological processes involved in the perception, encoding, storage, retrieval, and regulation of information about others and ourselves. This process is essential for survival and reproduction in complex social environments. Recent evidence suggests that impairments in social cognition frequently occur in schizophrenia, mainly contributing to poor functional outcomes, including the inability to engage in meaningful work and maintain satisfying interpersonal relationships. With the ambiguous definition of social cognition, the neurobiology underlying impaired social cognit...
Source: Neurobiology of Disease - November 1, 2018 Category: Neurology Authors: Kimoto S, Makinodan M, Kishimoto T Tags: Neurobiol Dis Source Type: research

Phenotypic and molecular features underlying neurodegeneration of motor neurons derived from spinal and bulbar muscular atrophy patients.
Abstract Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by the expansion of polyglutamine region in the androgen receptor. To gain insights into mechanisms of SBMA, four wild-type and five SBMA iPSC lines were differentiated to spinal motor neurons (sMNs) with high efficiency. SBMA sMNs showed neurite defects, reduced sMN survival and decreased protein synthesis levels. Microarray analysis revealed a dysregulation in various neuronal-related signalling pathways in SBMA sMNs. Strikingly, FAM135B a novel gene of unknown function, was found drastically downregulated in SBMA sMNs. Knoc...
Source: Neurobiology of Disease - October 31, 2018 Category: Neurology Authors: Sheila M, Narayanan G, Ma S, Tam WL, Chai J, Stanton LW Tags: Neurobiol Dis Source Type: research

Mice harbouring a SCA28 patient mutation in AFG3L2 develop late-onset ataxia associated with enhanced mitochondrial proteotoxicity.
E, Casari G, Altruda F, Turco E, Gasparre G, Battersby BJ, Porcelli AM, Ferrero E, Brusco A, Tempia F Abstract Spinocerebellar ataxia 28 is an autosomal dominant neurodegenerative disorder caused by missense mutations affecting the proteolytic domain of AFG3L2, a major component of the mitochondrial m-AAA protease. However, little is known of the underlying pathogenetic mechanisms or how to treat patients with SCA28. Currently available Afg3l2 mutant mice harbour deletions that lead to severe, early-onset neurological phenotypes that do not faithfully reproduce the late-onset and slowly progressing SCA28 phenotype...
Source: Neurobiology of Disease - October 30, 2018 Category: Neurology Authors: Mancini C, Hoxha E, Iommarini L, Brussino A, Richter U, Montarolo F, Cagnoli C, Parolisi R, Morosini DIG, Nicolò V, Maltecca F, Muratori L, Ronchi G, Geuna S, Arnaboldi F, Donetti E, Giorgio E, Cavalieri S, Di Gregorio E, Pozzi E, Ferrero M, Riberi E, Ca Tags: Neurobiol Dis Source Type: research

Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson's disease models.
Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson's disease models. Neurobiol Dis. 2018 Oct 28;: Authors: Weihofen A, Liu Y, Arndt JW, Huy C, Quan C, Smith BA, Baeriswyl JL, Cavegn N, Senn L, Su L, Marsh G, Auluck P, Montrasio F, Nitsch RM, Hirst WD, Cedarbaum JM, Blake Pepinsky R, Grimm J, Weinreb PH Abstract Aggregation of α-synuclein (α-syn) is neuropathologically and genetically linked to Parkinson's disease (PD). Since stereotypic cell-to-cell spreading of α-syn pathology is believed to contri...
Source: Neurobiology of Disease - October 28, 2018 Category: Neurology Authors: Weihofen A, Liu Y, Arndt JW, Huy C, Quan C, Smith BA, Baeriswyl JL, Cavegn N, Senn L, Su L, Marsh G, Auluck P, Montrasio F, Nitsch RM, Hirst WD, Cedarbaum JM, Blake Pepinsky R, Grimm J, Weinreb PH Tags: Neurobiol Dis Source Type: research

Role of intracellular Ca2+ stores for an impairment of visual processing in a mouse model of Alzheimer's disease.
Abstract Besides deficits in memory and cognition, impaired visual processing is common for Alzheimer's disease (AD) patients and mouse models of AD but underlying mechanisms still remain unclear. Using in vivo Ca2+ imaging of the mouse primary visual cortex (V1) we tested whether such impairment is caused by neuronal hyperactivity, an emerging functional hallmark of AD. Profound neuronal hyperactivity was indeed found in V1 of APPSWE/PS1G384A and even of PS1G384A mice, presenting neither with plaque accumulation nor with neuroinflammation. This hyperactivity was accompanied by over-responsiveness to visual stimul...
Source: Neurobiology of Disease - October 23, 2018 Category: Neurology Authors: Asavapanumas N, Brawek B, Martus P, Garaschuk O Tags: Neurobiol Dis Source Type: research

Enrichment of rare genetic variants in astrocyte gene enriched co-expression modules altered in postmortem brain samples of schizophrenia.
r MJG, Xu B Abstract The transcriptome profiles of the cingulate gyrus region from the postmortem brain tissues of a set of well-characterized patients with schizophrenia (SCZ) and matched controls were investigated using an integrated approach that analyzed both the alterations in transcription expression pattern and rare genetic variants in expressed genes. We demonstrated increased expression of astrocyte-related genes using spatiotemporal co-expression modules that have previously been established for developing human brain, and showed these results are independent of medication dosage. The relationship betwee...
Source: Neurobiology of Disease - October 19, 2018 Category: Neurology Authors: González-Peñas J, Costas J, Villamayor MJG, Xu B Tags: Neurobiol Dis Source Type: research

Glucagon-like peptide-2 reduces the obesity-associated inflammation in the brain.
In conclusion, the results of the present study suggest that GLP-2 stable analogue improves the obesity-associated neuroinflammation and the central stress conditions, it reduces the neuronal apoptotic death, providing evidence for a neuroprotective role of the peptide. PMID: 30347266 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - October 19, 2018 Category: Neurology Authors: Nuzzo D, Baldassano S, Amato A, Picone P, Galizzi G, Caldara GF, Di Carlo M, Mulè F Tags: Neurobiol Dis Source Type: research

PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by influencing synaptic function in the primary motor cortex of rats.
Abstract Proline-rich transmembrane protein 2 (PRRT2) was identified as the causative gene of paroxysmal kinesigenic choreoathetosis (PKC) as well as various other neurological diseases. However, the molecular mechanisms of how mutant PRRT2 leads to abnormal synaptic function and triggers PKC are still obscure. We generated a Prrt2 truncated mutant rat model which shows spontaneous PKC-like attacks with a relative low frequency as well as increased susceptibility to pentylenetetrazol (PTZ)-induced seizures. We demonstrate that PRRT2 is expressed on both pre- and post-synaptic membranes in the M1 cortex. PRRT2 nega...
Source: Neurobiology of Disease - October 19, 2018 Category: Neurology Authors: Mo J, Wang B, Zhu X, Wu X, Liu Y Tags: Neurobiol Dis Source Type: research

Pharmacological enhancement of retinoid-related orphan receptor α function mitigates spinocerebellar ataxia type 3 pathology.
Pharmacological enhancement of retinoid-related orphan receptor α function mitigates spinocerebellar ataxia type 3 pathology. Neurobiol Dis. 2018 Oct 18;: Authors: Watanave M, Hoshino C, Konno A, Fukuzaki Y, Matsuzaki Y, Ishitani T, Hirai H Abstract Cerebellar Purkinje cells (PCs) are the sole output neurons of the cerebellar cortex, and damage to PCs results in motor deficits. Spinocerebellar ataxia type 3 (SCA3, also known as Machado-Joseph disease), a hereditary neurodegenerative disease, is caused by an abnormal expansion of the polyglutamine tract in the causative ATXN3 protein. SCA3 affect...
Source: Neurobiology of Disease - October 18, 2018 Category: Neurology Authors: Watanave M, Hoshino C, Konno A, Fukuzaki Y, Matsuzaki Y, Ishitani T, Hirai H Tags: Neurobiol Dis Source Type: research

Autophagy in Neurological Diseases: An update.
PMID: 30342093 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - October 17, 2018 Category: Neurology Authors: Chu CT Tags: Neurobiol Dis Source Type: research

Distinct cytokine profiles in human brains resilient to Alzheimer's pathology.
sla T Abstract Our group has previously studied the brains of some unique individuals who are able to tolerate robust amounts of Alzheimer's pathological lesions (amyloid plaques and neurofibrillary tangles) without experiencing dementia while alive. These rare resilient cases do not demonstrate the patterns of neuronal/synaptic loss that are normally found in the brains of typical demented Alzheimer's patients. Moreover, they exhibit decreased astrocyte and microglial activation markers GFAP and CD68, suggesting that a suppressed neuroinflammatory response may be implicated in human brain resilience to Alzheimer'...
Source: Neurobiology of Disease - October 15, 2018 Category: Neurology Authors: Barroeta-Espar I, Weinstock LD, Perez-Nievas BG, Meltzer AC, Tick-Chong MS, Amaral AC, Murray ME, Moulder KL, Morris JC, Cairns NJ, Parisi JE, Lowe VJ, Petersen RC, Kofler J, Ikonomovic MD, López O, Klunk WE, Mayeux RP, Frosch MP, Wood LB, Gomez-Isla T Tags: Neurobiol Dis Source Type: research

Imaging biomarkers of epileptogenecity after traumatic brain injury - Preclinical frontiers.
Abstract Posttraumatic epilepsy (PTE) is a major neurodegenerative disease accounting for 20% of symptomatic epilepsy cases. A long latent phase offers a potential window for prophylactic treatment strategies to prevent epilepsy onset, provided that the patients at risk can be identified. Some promising imaging biomarker candidates for posttraumatic epileptogenesis have been identified, but more are required to provide the specificity and sensitivity for accurate prediction. Experimental models and preclinical longitudinal, multimodal imaging studies allow follow-up of complex cascade of events initiated by trauma...
Source: Neurobiology of Disease - October 12, 2018 Category: Neurology Authors: Immonen R, Harris NG, Wright D, Johnston L, Manninen E, Smith G, Paydar A, Branch C, Grohn O Tags: Neurobiol Dis Source Type: research

The gut microbiome and neuroinflammation in amyotrophic lateral sclerosis? Emerging clinical evidence.
PMID: 30321601 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - October 12, 2018 Category: Neurology Authors: Fournier CN, Houser M, Tansey MG, Glass JD, Hertzberg VS Tags: Neurobiol Dis Source Type: research

Preface.
PREFACE. Neurobiol Dis. 2018 Oct 09;: Authors: Galanopoulou AS, Engel J, Moshé SL PMID: 30312758 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - October 9, 2018 Category: Neurology Authors: Galanopoulou AS, Engel J, Moshé SL Tags: Neurobiol Dis Source Type: research

Endothelial cells promote excitatory synaptogenesis and improve ischemia-induced motor deficits in neonatal mice.
This study aims to investigate whether endothelial cells in the brain regulate postnatal synaptic development and to elucidate their role in functional recovery after ischemia. Here, we found that in vivo engraftment of endothelial cells increased synaptic puncta and excitatory postsynaptic currents in layers 2/3 of the motor cortex. This pro-synaptogenic effect was blocked by the depletion of VEGF in the grafted BMEC. The in vitro results showed that BMEC conditioned medium enhanced spine and synapse formation but conditioned medium without VEGF had no such effects. Moreover, under pathological conditions, transplanted en...
Source: Neurobiology of Disease - October 8, 2018 Category: Neurology Authors: Wu KW, Lv LL, Lei Y, Qian C, Sun FY Tags: Neurobiol Dis Source Type: research

Chemical biomarkers of epileptogenesis and ictogenesis in experimental epilepsy.
Abstract Epilepsy produces chronic chemical changes induced by altered cellular structures, and acute ones produced by conditions leading into individual seizures. Here, we aim to quantify 24 molecules simultaneously at baseline and during periods of lowered seizure threshold in rats. Using serial hippocampal microdialysis collections starting two weeks after the pilocarpine-induced status epilepticus, we evaluated how this chronic epilepsy model affects molecule levels and their interactions. Then, we quantified the changes occurring when the brain moves into a pro-seizure state using a novel model of physiologic...
Source: Neurobiology of Disease - October 7, 2018 Category: Neurology Authors: Luna-Munguia H, Zestos AG, Gliske SV, Kennedy RT, Stacey WC Tags: Neurobiol Dis Source Type: research

Melatonin as an adjunct to therapeutic hypothermia in a piglet model of neonatal encephalopathy: A translational study.
Abstract Therapeutic hypothermia is only partially protective for neonatal encephalopathy; there is an urgent need to develop treatments that augment cooling. Our objective was to assess safety, efficacy and pharmacokinetics of 5 and15 mg/kg/24 h melatonin (proprietary formulation) administered at 2 h and 26 h after hypoxia-ischemia (HI) with cooling in a piglet model. Following moderate cerebral HI, 30 piglets were eligible and randomized to: i) Hypothermia (33.5 °C, 2-26 h) and vehicle (HT + V;n = 13); b) HT and 5 mg/kg melatonin over 6 h at 2 h and 26 h after HI (HT + Mel-5;n...
Source: Neurobiology of Disease - October 6, 2018 Category: Neurology Authors: Robertson NJ, Martinello K, Lingam I, Avdic-Belltheus A, Meehan C, Alonso-Alconada D, Ragab S, Bainbridge A, Sokolowska M, Tachrout M, Middleton B, Price D, Hristova M, Golay X, Raschini AS, Aquino G, Pelizzi N, Facchinetti F Tags: Neurobiol Dis Source Type: research

Beneficial effects of n-3 polyunsaturated fatty acids administration in a partial lesion model of Parkinson's disease: The role of glia and NRf2 regulation.
ez RM Abstract Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been widely associated to beneficial effect over different neurodegenerative diseases. In the present study, we tested the potential therapeutic effect of docohexanoic acid (DHA) and its hydroxylated derivate, DHAH, in a partial lesion model of Parkinson's disease (PD). One month before and four months after the striatal lesion with 6-OHDA was made, the animals were daily treated with DHA (50 mg/kg), DHAH (50 mg/kg), vehicle or saline, by intragastric administration. Animal groups under n-3 PUFA treatments exhibited a trend to improve in amphe...
Source: Neurobiology of Disease - October 5, 2018 Category: Neurology Authors: Hernando S, Requejo C, Herran E, Ruiz-Ortega JA, Morera-Herreras T, Lafuente JV, Ugedo L, Gainza E, Pedraz JL, Igartua M, Hernández RM Tags: Neurobiol Dis Source Type: research

A potential gain-of-function variant of SLC9A6 leads to endosomal alkalinization and neuronal atrophy associated with Christianson Syndrome.
Abstract Loss-of-function mutations in the recycling endosomal (Na+,K+)/H+ exchanger gene SLC9A6/NHE6 result in overacidification and dysfunction of endosomal-lysosomal compartments, and cause a neurodevelopmental and degenerative form of X-linked intellectual disability called Christianson Syndrome (CS). However, knowledge of the disease heterogeneity of CS is limited. Here, we describe the clinical features and underlying molecular and cellular mechanisms associated with a CS patient carrying a de novo missense variant (p.Gly218Arg; G218R) of a conserved residue in its ion translocation domain that results in a ...
Source: Neurobiology of Disease - October 5, 2018 Category: Neurology Authors: Ilie A, Gao AYL, Boucher A, Park J, Berghuis AM, Hoffer MJV, Hilhorst-Hofstee Y, Anne McKinney R, Orlowski J Tags: Neurobiol Dis Source Type: research

Normalizing glucocorticoid levels attenuates metabolic and neuropathological symptoms in the R6/2 mouse model of huntington's disease.
Abstract Huntington's disease (HD) is a fatal genetic neurological disorder caused by a mutation in the human Huntingtin (HTT) gene. This mutation confers a toxic gain of function of the encoded mutant huntingtin (mHTT) protein, leading to widespread neuropathology including the formation of mHTT-positive inclusion bodies, gene dysregulation, reduced levels of adult dentate gyrus neurogenesis and ultimate neuron loss throughout many regions of the brain. Additionally, because HTT is ubiquitously expressed, several peripheral tissues are also affected. HD patients suffer from progressive motor, cognitive, psychiatr...
Source: Neurobiology of Disease - October 4, 2018 Category: Neurology Authors: Dufour BD, McBride JL Tags: Neurobiol Dis Source Type: research

Single-copy expression of an amyotrophic lateral sclerosis-linked TDP-43 mutation (M337V) in BAC transgenic mice leads to altered stress granule dynamics and progressive motor dysfunction.
Abstract Mutations in the gene encoding the RNA-binding protein TDP-43 cause amyotrophic lateral sclerosis (ALS), clinically and pathologically indistinguishable from the majority of 'sporadic' cases of ALS, establishing altered TDP-43 function and distribution as a primary mechanism of neurodegeneration. Transgenic mouse models in which TDP-43 is overexpressed only partially recapitulate the key cellular pathology of human ALS, but may also lead to non-specific toxicity. To avoid the potentially confounding effects of overexpression, and to maintain regulated spatio-temporal and cell-specific expression, we gener...
Source: Neurobiology of Disease - October 2, 2018 Category: Neurology Authors: Gordon D, Dafinca R, Scaber J, Alegre-Abarrategui J, Farrimond L, Scott C, Biggs D, Kent L, Oliver PL, Davies B, Ansorge O, Wade-Martins R, Talbot K Tags: Neurobiol Dis Source Type: research

Wwox deletion leads to reduced GABA-ergic inhibitory interneuron numbers and activation of microglia and astrocytes in mouse hippocampus.
This study provides the first genotype-phenotype observations as well as potential mechanistic clues associated with Wwox loss of function in the brain. PMID: 30290271 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - October 2, 2018 Category: Neurology Authors: Hussain T, Kil H, Hattiangady B, Lee J, Kodali M, Shuai B, Attaluri S, Takata Y, Shen J, Abba M, Shetty AK, Marcelo Aldaz C Tags: Neurobiol Dis Source Type: research

Ultra-micronized palmitoylethanolamide rescues the cognitive decline-associated loss of neural plasticity in the neuropathic mouse entorhinal cortex-dentate gyrus pathway.
Abstract Chronic pain is associated with cognitive deficits. Palmitoylethanolamide (PEA) has been shown to ameliorate pain and pain-related cognitive impairments by restoring glutamatergic synapses functioning in the spared nerve injury (SNI) of the sciatic nerve in mice. SNI reduced mechanical and thermal threshold, spatial memory and LTP at the lateral entorhinal cortex (LEC)-dentate gyrus (DG) pathway. It decreased also postsynaptic density, volume and dendrite arborization of DG and increased the expression of metabotropic glutamate receptor 1 and 7 (mGluR1 and mGluR7), of the GluR1, GluR1s845 and GluR1s831 su...
Source: Neurobiology of Disease - September 25, 2018 Category: Neurology Authors: Serena B, Claudia C, Rosaria R, Monica I, Carmela B, Antonio F, Francesca G, Fabiana P, Enza P, Mazzitelli M, Roberta I, Lea T, Vito N, Luigia C, Vincenzo DM, Antonio C, Sabatino M, Livio L Tags: Neurobiol Dis Source Type: research

Cyclophilin D deficiency attenuates mitochondrial F1Fo ATP synthase dysfunction via OSCP in Alzheimer's disease.
Abstract Mitochondrial dysfunction is pivotal in inducing synaptic injury and neuronal stress in Alzheimer's disease (AD). Mitochondrial F1Fo ATP synthase deregulation is a hallmark mitochondrial defect leading to oxidative phosphorylation (OXPHOS) failure in this neurological disorder. Oligomycin sensitivity conferring protein (OSCP) is a crucial F1Fo ATP synthase subunit. Decreased OSCP levels and OSCP interaction with amyloid β (Aβ) constitute key aspects of F1Fo ATP synthase pathology in AD-related conditions. However, the detailed mechanisms promoting such AD-related OSCP changes have not been fully...
Source: Neurobiology of Disease - September 25, 2018 Category: Neurology Authors: Gauba E, Chen H, Guo L, Du H Tags: Neurobiol Dis Source Type: research

TSPO and amyloid deposits in sub-regions of the hippocampus in the 3xTgAD mouse model of Alzheimer's disease.
Millet P Abstract The involvement of the 18kDa translocator protein (TSPO), a marker of neuroinflammation, in Alzheimer's disease (AD) remains controversial. In the present report, we used [125I]-CLINDE, a SPECT TSPO radiotracer never before used in AD, and we investigated the relationship between TSPO and amyloid plaque density (using [125I]-DRM106) in a triple transgenic mouse model of AD (3xTgAD, APPSWE, PS1M146V and TauP301L). Our results show that TSPO increases appear before those of amyloid deposits. Moreover, the different parts of the hippocampus are differentially affected. Indeed, for both TSPO and amy...
Source: Neurobiology of Disease - September 24, 2018 Category: Neurology Authors: Tournier BB, Tsartsalis S, Rigaud D, Fossey C, Cailly T, Fabis F, Pham T, Grégoire MC, Kövari E, Moulin-Sallanon M, Savioz A, Millet P Tags: Neurobiol Dis Source Type: research

5alpha-reductase inhibitors dampen L-DOPA-induced dyskinesia via normalization of dopamine D1-receptor signaling pathway and D1-D3 receptor interaction.
Abstract Although 1-3,4-dihydroxyphenylalanine (L-DOPA) is the mainstay therapy for treating Parkinson's disease (PD), its long-term administration is accompanied by the development of motor complications, particularly L-DOPA induced dyskinesia (LID), that dramatically affects patients' quality of life. LID has consistently been related to an excessive dopamine receptor transmission, particularly at the down-stream signaling of the striatal D1 receptors (D1R), resulting in an exaggerated stimulation of cAMP-dependent protein kinase and extracellular signal-regulated kinase (ERK) pathway. We previously reported tha...
Source: Neurobiology of Disease - September 24, 2018 Category: Neurology Authors: Fanni S, Scheggi S, Rossi F, Tronci E, Traccis F, Stancampiano R, De Montis MG, Devoto P, Gambarana C, Bortolato M, Frau R, Carta M Tags: Neurobiol Dis Source Type: research

NMDA receptor GluN2D subunit participates to levodopa-induced dyskinesia pathophysiology.
Abstract In the striatum, specific N-methyl-d-aspartate receptor (NMDAR) subtypes are found in different neuronal cells. Spiny projection neurons (SPNs) are characterized by NMDARs expressing GluN2A and GluN2B subunits, while GluN2D is exclusively detected in striatal cholinergic interneurons (ChIs). In Parkinson's disease (PD), dopamine depletion and prolonged treatment with levodopa (L-DOPA) trigger adaptive changes in the glutamatergic transmission from the cortex to the striatum, also resulting in the aberrant function of striatal NMDARs. While modifications of GluN2A- and GluN2B-NMDARs in SPNs have been exten...
Source: Neurobiology of Disease - September 24, 2018 Category: Neurology Authors: Mellone M, Zianni E, Stanic J, Campanelli F, Marino G, Ghiglieri V, Longhi A, Thiolat ML, Li Q, Calabresi P, Bezard E, Picconi B, Di Luca M, Gardoni F Tags: Neurobiol Dis Source Type: research

Degeneration of cholinergic basal forebrain nuclei after focally evoked status epilepticus.
Abstract Status epilepticus of limbic onset might cause degenerative phenomena in different brain structures, and may be associated with chronic cognitive and EEG effects. In the present study SE was evoked focally by microinfusing picomolar doses of cyclothiazide+bicuculline into the anterior extent of the piriform cortex (APC) in rats, the so-called area tempestas, an approach which allows to evaluate selectively the effects of seizure spreading through the natural anatomical circuitries up to secondary generalization. In the brain of rats submitted to SE we analyzed neuronal density, occurrence of degenerative ...
Source: Neurobiology of Disease - September 20, 2018 Category: Neurology Authors: Biagioni F, Gaglione A, Giorgi FS, Bucci D, Mojanova S, De Fusco A, Madonna M, Fornai F Tags: Neurobiol Dis Source Type: research

Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation-inhibition imbalance.
Abstract Prader-Willi and the related Schaaf-Yang Syndromes (PWS/SYS) are rare neurodevelopmental disorders characterized by overlapping phenotypes of high incidence of autism spectrum disorders (ASD) and neonatal feeding difficulties. Based on clinical and basic studies, oxytocin pathway defects are suggested to contribute disease pathogenesis but the mechanism has been poorly understood. Specifically, whether the impairment in oxytocin system is limited to neuropeptide levels and how the functional properties of broader oxytocin neuron circuits affected in PWS/SYS have not been addressed. Using cell type specifi...
Source: Neurobiology of Disease - September 18, 2018 Category: Neurology Authors: Ates T, Oncul M, Dilsiz P, Topcu IC, Civas CC, Alp MI, Aklan I, Oz EA, Yavuz Y, Yilmaz B, Atasoy NS, Atasoy D Tags: Neurobiol Dis Source Type: research

Path mediation analysis reveals GBA impacts Lewy body disease status by increasing α-synuclein levels.
In conclusion, we show that the introduced immuno-based assays enable the quantitative assessment of glucocerebrosidase and α-synuclein parameters in post-mortem brain. In the substantia nigra, reduced glucocerebrosidase levels contribute to the increase in α-synuclein levels and to PD-DLB disease manifestation partly by increasing its glycolipid substrate glucosylsphingosine. This interrelation between glucocerebrosidase, glucosylsphingosine and α-synuclein parameters supports the hypothesis that glucocerebrosidase acts as a modulator of PD-DLB. PMID: 30236861 [PubMed - as supplied by publisher] (So...
Source: Neurobiology of Disease - September 17, 2018 Category: Neurology Authors: Gündner AL, Duran-Pacheco G, Zimmermann S, Ruf I, Moors T, Baumann K, Jagasia R, van de Berg WDJ, Kremer T Tags: Neurobiol Dis Source Type: research

The PPARGC1A locus and CNS-specific PGC-1 α isoforms are associated with Parkinson's Disease.
The PPARGC1A locus and CNS-specific PGC-1α isoforms are associated with Parkinson's Disease. Neurobiol Dis. 2018 Sep 17;: Authors: Soyal SM, Zara G, Ferger B, Felder TK, Kwik M, Nofziger C, Dossena S, Schwienbacher C, Hicks AA, Pramstaller PP, Paulmichl M, Weis S, Patsch W Abstract Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. PGC-1α, encoded by PPARGC1A, is a transcriptional co-activator that has been implicated in the pathogenesis of neurodegenerative disorders. We recently discovered multiple new PPARGC1A transcripts that initiate from a novel p...
Source: Neurobiology of Disease - September 17, 2018 Category: Neurology Authors: Soyal SM, Zara G, Ferger B, Felder TK, Kwik M, Nofziger C, Dossena S, Schwienbacher C, Hicks AA, Pramstaller PP, Paulmichl M, Weis S, Patsch W Tags: Neurobiol Dis Source Type: research

The characteristics of pallidal low-frequency and beta bursts could help implementing adaptive brain stimulation in the parkinsonian and dystonic internal globus pallidus.
CONCLUSION: Pallidal LF and beta burst amplitudes have different characteristics in PD and dystonia. The presence of increased burst amplitudes could be employed as feedback for GPi-aDBS. PMID: 30227227 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - September 15, 2018 Category: Neurology Authors: Piña-Fuentes D, van Zijl JC, van Dijk JMC, Little S, Tinkhauser G, Marinus Oterdoom DL, Tijssen MAJ, Beudel M Tags: Neurobiol Dis Source Type: research

Stem cell therapy for neurological disorders: A focus on aging.
Abstract Age-related neurological disorders continue to pose a significant societal and economic burden. Aging is a complex phenomenon that affects many aspects of the human body. Specifically, aging can have detrimental effects on the progression of brain diseases and endogenous stem cells. Stem cell therapies possess promising potential to mitigate the neurological symptoms of such diseases. However, aging presents a major obstacle for maximum efficacy of these treatments. In this review, we discuss current preclinical and clinical literature to highlight the interactions between aging, stem cell therapy, and th...
Source: Neurobiology of Disease - September 13, 2018 Category: Neurology Authors: Nguyen H, Zarriello S, Coats A, Nelson C, Kingsbury C, Gorsky A, Rajani M, Neal EG, Borlongan CV Tags: Neurobiol Dis Source Type: research

Accelerated accumulation of retinal α-synuclein (pSer129) and tau, neuroinflammation and autophagic dysregulation in a seeded mouse model of Parkinson's disease.
This study describes retinal pathology resulting from the A53T mutation. We show that seeding with brain homogenates from old TgM83 mice accelerates retinal pathology. We demonstrate that Raman spectroscopy can be used to accurately identify a diseased retina based on its biochemical profile, and that α-synuclein accumulation may contribute to accumulation of pTauThr231 proteins, neuroinflammation, metabolic dysregulation, and photoreceptor cell death. Our work provides insight into retinal changes associated with Parkinson's disease, and may contribute to a better understanding of visual symptoms experienced by pati...
Source: Neurobiology of Disease - September 12, 2018 Category: Neurology Authors: Mammadova N, Summers CM, Kokemuller RD, He Q, Ding S, Baron T, Yu C, Valentine RJ, Sakaguchi DS, Kanthasamy AG, Greenlee JJ, Heather West Greenlee M Tags: Neurobiol Dis Source Type: research

Post-stroke administration of omega-3 polyunsaturated fatty acids promotes neurovascular restoration after ischemic stroke in mice: Efficacy declines with aging.
Abstract Post-stroke treatment with omega-3 polyunsaturated fatty acids (n-3 PUFAs) may be a promising therapy in young animals but this has not been tested in aged subjects, a population at most risk of ischemic stroke. Herein we examined the therapeutic efficacy of n-3 PUFAs after distal middle cerebral artery occlusion (dMCAO) in young (10-12 weeks old) and aged (18 months old) mice. Post-ischemic mice were randomly assigned to 4 groups that received: 1) regular food with low content of n-3 PUFAs, 2) intraperitoneal docosahexaenoic acid (DHA, a major component of n-3 PUFAs) injections, 3) Fish oil (FO, cont...
Source: Neurobiology of Disease - September 12, 2018 Category: Neurology Authors: Jiang X, Suenaga J, Pu H, Wei Z, Smith AD, Hu X, Shi Y, Chen J Tags: Neurobiol Dis Source Type: research

Mitochondria and neuroprotection in stroke: Cationic arginine-rich peptides (CARPs) as a novel class of mitochondria-targeted neuroprotective therapeutics.
Abstract Stroke is the second leading cause of death globally and represents a major cause of devastating long-term disability. Despite sustained efforts to develop clinically effective neuroprotective therapies, presently there is no clinically available neuroprotective agent for stroke. As a central mediator of neurodamaging events in stroke, mitochondria are recognised as a critical neuroprotective target, and as such, provide a focus for developing mitochondrial-targeted therapeutics. In recent years, cationic arginine-rich peptides (CARPs) have been identified as a novel class of neuroprotective agent with se...
Source: Neurobiology of Disease - September 12, 2018 Category: Neurology Authors: MacDougall G, Anderton RS, Mastaglia FL, Knuckey NW, Meloni BP Tags: Neurobiol Dis Source Type: research

What is the functional relevance of reorganization in primary motor cortex after spinal cord injury?
Abstract Motor output maps within primary motor cortex are widely distributed and modified by motor skill learning and neurological injury. Functions that these maps represent after spinal cord injury remain debatable. Moreover, the pattern of reorganization and whether it supports recovery of compromised motor function is not well understood. A deeper understanding of the pathophysiological mechanisms of motor dysfunction after spinal cord injury is necessary to develop and optimize repair strategies. There are three purposes for this review. The first is to synthesize available research on spontaneous reorganiza...
Source: Neurobiology of Disease - September 11, 2018 Category: Neurology Authors: Urbin MA, Royston DA, Weber DJ, Boninger ML, Collinger JL Tags: Neurobiol Dis Source Type: research

Assessment of the effects of transthyretin peptide inhibitors in Drosophila models of neuropathic ATTR.
PMID: 30213731 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - September 10, 2018 Category: Neurology Authors: Saelices L, Pokrzywa M, Pawelek K, Eisenberg DS Tags: Neurobiol Dis Source Type: research

Increased bioavailability of cyclic guanylate monophosphate prevents retinal ganglion cell degeneration.
Abstract The nitric oxide - guanylyl cyclase-1 - cyclic guanylate monophosphate (NO-GC-1-cGMP) pathway has emerged as a potential pathogenic mechanism for glaucoma, a common intraocular pressure (IOP)-related optic neuropathy characterized by the degeneration of retinal ganglion cells (RGCs) and their axons in the optic nerve. NO activates GC-1 to increase cGMP levels, which are lowered by cGMP-specific phosphodiesterase (PDE) activity. This pathway appears to play a role in both the regulation of IOP, where reduced cGMP levels in mice leads to elevated IOP and subsequent RGC degeneration. Here, we investigated wh...
Source: Neurobiology of Disease - September 10, 2018 Category: Neurology Authors: Wareham LK, Dordea AC, Schleifer G, Yao V, Batten A, Fei F, Mertz J, Gregory-Ksander M, Pasquale LR, Sappington RM, Buys ES Tags: Neurobiol Dis Source Type: research