CHCHD10 < sup > S59L/+ < /sup > mouse model: Behavioral and neuropathological features of frontotemporal dementia
Neurobiol Dis. 2024 Apr 5:106498. doi: 10.1016/j.nbd.2024.106498. Online ahead of print.ABSTRACTCHCHD10-related disease causes a spectrum of clinical presentations including mitochondrial myopathy, cardiomyopathy, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We generated a knock-in mouse model bearing the p.Ser59Leu (S59L) CHCHD10 variant. Chchd10S59L/+ mice have been shown to phenotypically replicate the disorders observed in patients: myopathy with mtDNA instability, cardiomyopathy and typical ALS features (protein aggregation, neuromuscular junction degeneration and spinal motor neuron loss). H...
Source: Neurobiology of Disease - April 7, 2024 Category: Neurology Authors: Emmanuelle C Genin Pauline Pozzo di Borgo Thomas Lorivel Sandrine Hugues M élissa Farinelli Alessandra Mauri-Crouzet Fran çoise Lespinasse Lucas Godin V éronique Paquis-Flucklinger Agn ès Petit-Paitel Source Type: research
Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy
In this study, we first showed that human DI-CMTC-causing TyrRSE196K mis-interacts with the extracellular domain of the BDNF receptor TrkB, an aberrant association we have previously characterised for several mutant glycyl-tRNA synthetases linked to CMT type 2D (CMT2D). We then performed temporal neuromuscular assessments of YarsE196K mice modelling DI-CMT. We determined that YarsE196K homozygotes display a selective, age-dependent impairment in in vivo axonal transport of neurotrophin-containing signalling endosomes, phenocopying CMT2D mice. This impairment is replicated by injection of recombinant TyrRSE196K, but not Tyr...
Source: Neurobiology of Disease - April 7, 2024 Category: Neurology Authors: Elena R Rhymes Rebecca L Simkin Ji Qu David Villarroel-Campos Sunaina Surana Yao Tong Ryan Shapiro Robert W Burgess Xiang-Lei Yang Giampietro Schiavo James N Sleigh Source Type: research
Genetic and pathological features encipher the phenotypic heterogeneity of Gerstmann-Str äussler-Scheinker disease
CONCLUSION: This study reveals GSS's intricate nature, showing significant variations in clinical presentations, diagnostic findings, and pathological features. Mutation sites and pathological changes play crucial roles in determining the GSS clinical heterogeneity.PMID:38583641 | DOI:10.1016/j.nbd.2024.106497 (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - April 7, 2024 Category: Neurology Authors: Zhongyun Chen Yu Kong Jing Zhang Wen-Quan Zou Liyong Wu Source Type: research
Spatio-temporal brain invasion pattern of Streptococcus pneumoniae and dynamic changes in the cellular environment in bacteremia-derived meningitis
Neurobiol Dis. 2024 Apr 5:106484. doi: 10.1016/j.nbd.2024.106484. Online ahead of print.ABSTRACTStreptococcus pneumoniae (the pneumococcus) is the major cause of bacterial meningitis globally, and pneumococcal meningitis is associated with increased risk of long-term neurological sequelae. These include several sensorimotor functions that are controlled by specific brain regions which, during bacterial meningitis, are damaged by a neuroinflammatory response and the deleterious action of bacterial toxins in the brain. However, little is known about the invasion pattern of the pneumococcus into the brain. Using a bacteremia-...
Source: Neurobiology of Disease - April 7, 2024 Category: Neurology Authors: Kristine Farmen Miguel Tofi ño-Vian Katrin Wellfelt Lars Olsson Federico Iovino Source Type: research
CHCHD10 < sup > S59L/+ < /sup > mouse model: Behavioral and neuropathological features of frontotemporal dementia
Neurobiol Dis. 2024 Apr 5:106498. doi: 10.1016/j.nbd.2024.106498. Online ahead of print.ABSTRACTCHCHD10-related disease causes a spectrum of clinical presentations including mitochondrial myopathy, cardiomyopathy, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We generated a knock-in mouse model bearing the p.Ser59Leu (S59L) CHCHD10 variant. Chchd10S59L/+ mice have been shown to phenotypically replicate the disorders observed in patients: myopathy with mtDNA instability, cardiomyopathy and typical ALS features (protein aggregation, neuromuscular junction degeneration and spinal motor neuron loss). H...
Source: Neurobiology of Disease - April 7, 2024 Category: Neurology Authors: Emmanuelle C Genin Pauline Pozzo di Borgo Thomas Lorivel Sandrine Hugues M élissa Farinelli Alessandra Mauri-Crouzet Fran çoise Lespinasse Lucas Godin V éronique Paquis-Flucklinger Agn ès Petit-Paitel Source Type: research
Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy
In this study, we first showed that human DI-CMTC-causing TyrRSE196K mis-interacts with the extracellular domain of the BDNF receptor TrkB, an aberrant association we have previously characterised for several mutant glycyl-tRNA synthetases linked to CMT type 2D (CMT2D). We then performed temporal neuromuscular assessments of YarsE196K mice modelling DI-CMT. We determined that YarsE196K homozygotes display a selective, age-dependent impairment in in vivo axonal transport of neurotrophin-containing signalling endosomes, phenocopying CMT2D mice. This impairment is replicated by injection of recombinant TyrRSE196K, but not Tyr...
Source: Neurobiology of Disease - April 7, 2024 Category: Neurology Authors: Elena R Rhymes Rebecca L Simkin Ji Qu David Villarroel-Campos Sunaina Surana Yao Tong Ryan Shapiro Robert W Burgess Xiang-Lei Yang Giampietro Schiavo James N Sleigh Source Type: research
Genetic and pathological features encipher the phenotypic heterogeneity of Gerstmann-Str äussler-Scheinker disease
CONCLUSION: This study reveals GSS's intricate nature, showing significant variations in clinical presentations, diagnostic findings, and pathological features. Mutation sites and pathological changes play crucial roles in determining the GSS clinical heterogeneity.PMID:38583641 | DOI:10.1016/j.nbd.2024.106497 (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - April 7, 2024 Category: Neurology Authors: Zhongyun Chen Yu Kong Jing Zhang Wen-Quan Zou Liyong Wu Source Type: research
Spatio-temporal brain invasion pattern of Streptococcus pneumoniae and dynamic changes in the cellular environment in bacteremia-derived meningitis
Neurobiol Dis. 2024 Apr 5:106484. doi: 10.1016/j.nbd.2024.106484. Online ahead of print.ABSTRACTStreptococcus pneumoniae (the pneumococcus) is the major cause of bacterial meningitis globally, and pneumococcal meningitis is associated with increased risk of long-term neurological sequelae. These include several sensorimotor functions that are controlled by specific brain regions which, during bacterial meningitis, are damaged by a neuroinflammatory response and the deleterious action of bacterial toxins in the brain. However, little is known about the invasion pattern of the pneumococcus into the brain. Using a bacteremia-...
Source: Neurobiology of Disease - April 7, 2024 Category: Neurology Authors: Kristine Farmen Miguel Tofi ño-Vian Katrin Wellfelt Lars Olsson Federico Iovino Source Type: research
Phenotypic analysis of multielectrode array EEG biomarkers in developing and adult male Fmr1 KO mice
Neurobiol Dis. 2024 Apr 4:106496. doi: 10.1016/j.nbd.2024.106496. Online ahead of print.ABSTRACTFragile X Syndrome (FXS) is a leading known genetic cause of intellectual disability with symptoms that include increased anxiety and social and sensory processing deficits. Recent electroencephalographic (EEG) studies in humans with FXS have identified neural oscillation deficits that include increased resting state gamma power, increased amplitude of auditory evoked potentials, and reduced phase locking of sound-evoked gamma oscillations. Similar EEG phenotypes are present in mouse models of FXS, but very little is known about...
Source: Neurobiology of Disease - April 6, 2024 Category: Neurology Authors: Carrie R Jonak Samantha A Assad Manbir S Sandhu Terese A Garcia Jeffrey A Rumschlag Khaleel A Razak Devin K Binder Source Type: research
Aberrant dynamic functional network connectivity in progressive supranuclear palsy
DISCUSSION: Our findings were that the altered connectivity was mostly concentrated in the CBN and MO. In addition, PSP patients had different temporal dynamics, which were associated with bulbar and oculomotor symptoms in PSPRS. It suggest that variations in dynamic functional network connectivity properties may represent an essential neurological mechanism in PSP.PMID:38579913 | DOI:10.1016/j.nbd.2024.106493 (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - April 5, 2024 Category: Neurology Authors: Junyu Qu Min Tian Rui Zhu Chengyuan Song Yongsheng Wu Guihua Xu Yiming Liu Dawei Wang Source Type: research
Aberrant dynamic functional network connectivity in progressive supranuclear palsy
DISCUSSION: Our findings were that the altered connectivity was mostly concentrated in the CBN and MO. In addition, PSP patients had different temporal dynamics, which were associated with bulbar and oculomotor symptoms in PSPRS. It suggest that variations in dynamic functional network connectivity properties may represent an essential neurological mechanism in PSP.PMID:38579913 | DOI:10.1016/j.nbd.2024.106493 (Source: Neurobiology of Disease)
Source: Neurobiology of Disease - April 5, 2024 Category: Neurology Authors: Junyu Qu Min Tian Rui Zhu Chengyuan Song Yongsheng Wu Guihua Xu Yiming Liu Dawei Wang Source Type: research
Spatial omics reveals molecular changes in focal cortical dysplasia type II
Neurobiol Dis. 2024 Apr 2:106491. doi: 10.1016/j.nbd.2024.106491. Online ahead of print.ABSTRACTFocal cortical dysplasia (FCD) represents a group of diverse localized cortical lesions that are highly epileptogenic and occur due to abnormal brain development caused by genetic mutations, involving the mammalian target of rapamycin (mTOR). These somatic mutations lead to mosaicism in the affected brain, posing challenges to unravel the direct and indirect functional consequences of these mutations. To comprehensively characterize the impact of mTOR mutations on the brain, we employed here a multimodal approach in a preclinica...
Source: Neurobiology of Disease - April 4, 2024 Category: Neurology Authors: Isabeau Vermeulen Natalia Rodriguez-Alvarez Liesbeth Fran çois Delphine Viot Fariba Poosti Eleonora Aronica Stefanie Dedeurwaerdere Patrick Barton Berta Cillero-Pastor Ron M A Heeren Source Type: research
Phenotypical, genotypical and pathological characterization of the moonwalker mouse, a model of ataxia
Neurobiol Dis. 2024 Apr 2;195:106492. doi: 10.1016/j.nbd.2024.106492. Online ahead of print.ABSTRACTWe performed a comprehensive study of the morphological, functional, and genetic features of moonwalker (MWK) mice, a mouse model of spinocerebellar ataxia caused by a gain of function of the TRPC3 channel. These mice show numerous behavioral symptoms including tremor, altered gait, circling behavior, impaired motor coordination, impaired motor learning and decreased limb strength. Cerebellar pathology is characterized by early and almost complete loss of unipolar brush cells as well as slowly progressive, moderate loss of P...
Source: Neurobiology of Disease - April 4, 2024 Category: Neurology Authors: Gabriella Sekerkov á S ümeyra Kiliç Yen-Hsin Cheng Natalie Fredrick Anne Osmani Haram Kim Puneet Opal Marco Martina Source Type: research
Spatial omics reveals molecular changes in focal cortical dysplasia type II
Neurobiol Dis. 2024 Apr 2:106491. doi: 10.1016/j.nbd.2024.106491. Online ahead of print.ABSTRACTFocal cortical dysplasia (FCD) represents a group of diverse localized cortical lesions that are highly epileptogenic and occur due to abnormal brain development caused by genetic mutations, involving the mammalian target of rapamycin (mTOR). These somatic mutations lead to mosaicism in the affected brain, posing challenges to unravel the direct and indirect functional consequences of these mutations. To comprehensively characterize the impact of mTOR mutations on the brain, we employed here a multimodal approach in a preclinica...
Source: Neurobiology of Disease - April 4, 2024 Category: Neurology Authors: Isabeau Vermeulen Natalia Rodriguez-Alvarez Liesbeth Fran çois Delphine Viot Fariba Poosti Eleonora Aronica Stefanie Dedeurwaerdere Patrick Barton Berta Cillero-Pastor Ron M A Heeren Source Type: research
Phenotypical, genotypical and pathological characterization of the moonwalker mouse, a model of ataxia
Neurobiol Dis. 2024 Apr 2:106492. doi: 10.1016/j.nbd.2024.106492. Online ahead of print.ABSTRACTWe performed a comprehensive study of the morphological, functional, and genetic features of moonwalker (MWK) mice, a mouse model of spinocerebellar ataxia caused by a gain of function of the TRPC3 channel. These mice show numerous behavioral symptoms including tremor, altered gait, circling behavior, impaired motor coordination, impaired motor learning and decreased limb strength. Cerebellar pathology is characterized by early and almost complete loss of unipolar brush cells as well as slowly progressive, moderate loss of Purki...
Source: Neurobiology of Disease - April 4, 2024 Category: Neurology Authors: Gabriella Sekerkov á S ümeyra Kiliç Yen-Hsin Cheng Natalie Fredrick Anne Osmani Haram Kim Puneet Opal Marco Martina Source Type: research
