Proteomic analysis of X-linked dystonia parkinsonism disease striatal neurons reveals altered RNA metabolism and splicing
Neurobiol Dis. 2023 Nov 30:106367. doi: 10.1016/j.nbd.2023.106367. Online ahead of print.ABSTRACTX-linked dystonia-parkinsonism (XDP) is a rare neurodegenerative disease endemic to the Philippines. The genetic cause for XDP is an insertion of a SINE-VNTR-Alu (SVA)-type retrotransposon within intron 32 of TATA-binding protein associated factor 1 (TAF1) that causes an alteration of TAF1 splicing, partial intron retention, and decreased transcription. Although TAF1 is expressed in all organs, medium spiny neurons (MSNs) within the striatum are one of the cell types most affected in XDP. To define how mutations in the TAF1 gen...
Source: Neurobiology of Disease - December 2, 2023 Category: Neurology Authors: Kizito-Tshitoko Tshilenge Joanna Bons Carlos Galicia Aguirre Cristian Geronimo-Olvera Samah Shah Jacob Rose Akos A Gerencser Sally K Mak Michelle E Ehrlich D Cristopher Bragg Birgit Schilling Lisa M Ellerby Source Type: research
Antisense oligonucleotide-mediated disruption of HTT caspase-6 cleavage site ameliorates the phenotype of YAC128 Huntington disease mice
Neurobiol Dis. 2023 Nov 29:106368. doi: 10.1016/j.nbd.2023.106368. Online ahead of print.ABSTRACTIn Huntington disease, cellular toxicity is particularly caused by toxic protein fragments generated from the mutant huntingtin (HTT) protein. By modifying the HTT protein, we aim to reduce proteolytic cleavage and ameliorate the consequences of mutant HTT without lowering total HTT levels. To that end, we use an antisense oligonucleotide (AON) that targets HTT pre-mRNA and induces partial skipping of exon 12, which contains the critical caspase-6 cleavage site. Here, we show that AON-treatment can partially restore the phenoty...
Source: Neurobiology of Disease - December 1, 2023 Category: Neurology Authors: Elsa C Kuijper Maurice Overzier Ernst Suidgeest Oleh Dzyubachyk Cecile Maguin Jean-Baptiste P érot Julien Flament Yavuz Ariyurek Hailiang Mei Ronald A M Buijsen Louise van der Weerd Willeke van Roon-Mom Source Type: research
Antisense oligonucleotide-mediated disruption of HTT caspase-6 cleavage site ameliorates the phenotype of YAC128 Huntington disease mice
Neurobiol Dis. 2023 Nov 29:106368. doi: 10.1016/j.nbd.2023.106368. Online ahead of print.ABSTRACTIn Huntington disease, cellular toxicity is particularly caused by toxic protein fragments generated from the mutant huntingtin (HTT) protein. By modifying the HTT protein, we aim to reduce proteolytic cleavage and ameliorate the consequences of mutant HTT without lowering total HTT levels. To that end, we use an antisense oligonucleotide (AON) that targets HTT pre-mRNA and induces partial skipping of exon 12, which contains the critical caspase-6 cleavage site. Here, we show that AON-treatment can partially restore the phenoty...
Source: Neurobiology of Disease - December 1, 2023 Category: Neurology Authors: Elsa C Kuijper Maurice Overzier Ernst Suidgeest Oleh Dzyubachyk Cecile Maguin Jean-Baptiste P érot Julien Flament Yavuz Ariyurek Hailiang Mei Ronald A M Buijsen Louise van der Weerd Willeke van Roon-Mom Source Type: research
Ganglioglioma cells potentiate neuronal network synchronicity and elicit burst discharges via released factors
Neurobiol Dis. 2023 Nov 24:106364. doi: 10.1016/j.nbd.2023.106364. Online ahead of print.ABSTRACTGangliogliomas (GGs) represent the most frequent glioneuronal tumor entity associated with chronic recurrent seizures; rare anaplastic GGs variants retain the glioneuronal character. So far, key mechanisms triggering chronic hyperexcitability in the peritumoral area are unresolved. Based on a recent mouse model for anaplastic GG (BRAFV600E, mTOR activation and Trp53KO) we here assessed the influence of GG-secreted factors on non-neoplastic cells in-vitro. We generated conditioned medium (CM) from primary GG cell cultures to dev...
Source: Neurobiology of Disease - November 26, 2023 Category: Neurology Authors: Philipp M üller Dirk Dietrich Susanne Schoch Julika Pitsch Albert J Becker Silvia Cases-Cunillera Source Type: research
Ganglioglioma cells potentiate neuronal network synchronicity and elicit burst discharges via released factors
Neurobiol Dis. 2023 Nov 24:106364. doi: 10.1016/j.nbd.2023.106364. Online ahead of print.ABSTRACTGangliogliomas (GGs) represent the most frequent glioneuronal tumor entity associated with chronic recurrent seizures; rare anaplastic GGs variants retain the glioneuronal character. So far, key mechanisms triggering chronic hyperexcitability in the peritumoral area are unresolved. Based on a recent mouse model for anaplastic GG (BRAFV600E, mTOR activation and Trp53KO) we here assessed the influence of GG-secreted factors on non-neoplastic cells in-vitro. We generated conditioned medium (CM) from primary GG cell cultures to dev...
Source: Neurobiology of Disease - November 26, 2023 Category: Neurology Authors: Philipp M üller Dirk Dietrich Susanne Schoch Julika Pitsch Albert J Becker Silvia Cases-Cunillera Source Type: research
Ganglioglioma cells potentiate neuronal network synchronicity and elicit burst discharges via released factors
Neurobiol Dis. 2023 Nov 24:106364. doi: 10.1016/j.nbd.2023.106364. Online ahead of print.ABSTRACTGangliogliomas (GGs) represent the most frequent glioneuronal tumor entity associated with chronic recurrent seizures; rare anaplastic GGs variants retain the glioneuronal character. So far, key mechanisms triggering chronic hyperexcitability in the peritumoral area are unresolved. Based on a recent mouse model for anaplastic GG (BRAFV600E, mTOR activation and Trp53KO) we here assessed the influence of GG-secreted factors on non-neoplastic cells in-vitro. We generated conditioned medium (CM) from primary GG cell cultures to dev...
Source: Neurobiology of Disease - November 26, 2023 Category: Neurology Authors: Philipp M üller Dirk Dietrich Susanne Schoch Julika Pitsch Albert J Becker Silvia Cases-Cunillera Source Type: research
Ganglioglioma cells potentiate neuronal network synchronicity and elicit burst discharges via released factors
Neurobiol Dis. 2023 Nov 24:106364. doi: 10.1016/j.nbd.2023.106364. Online ahead of print.ABSTRACTGangliogliomas (GGs) represent the most frequent glioneuronal tumor entity associated with chronic recurrent seizures; rare anaplastic GGs variants retain the glioneuronal character. So far, key mechanisms triggering chronic hyperexcitability in the peritumoral area are unresolved. Based on a recent mouse model for anaplastic GG (BRAFV600E, mTOR activation and Trp53KO) we here assessed the influence of GG-secreted factors on non-neoplastic cells in-vitro. We generated conditioned medium (CM) from primary GG cell cultures to dev...
Source: Neurobiology of Disease - November 26, 2023 Category: Neurology Authors: Philipp M üller Dirk Dietrich Susanne Schoch Julika Pitsch Albert J Becker Silvia Cases-Cunillera Source Type: research
Characterisation and prion transmission study in mice with genetic reduction of sporadic Creutzfeldt-Jakob disease risk gene Stx6
Neurobiol Dis. 2023 Nov 21:106363. doi: 10.1016/j.nbd.2023.106363. Online ahead of print.ABSTRACTSporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is thought to occur when the cellular prion protein (PrPC) spontaneously misfolds and assembles into prion fibrils, culminating in fatal neurodegeneration. In a genome-wide association study of sCJD, we recently identified risk variants in and around the gene STX6, with evidence to suggest a causal increase of STX6 expression in disease-relevant brain regions. STX6 encodes syntaxin-6, a SNARE protein primarily involved in early endosome to trans-Gol...
Source: Neurobiology of Disease - November 23, 2023 Category: Neurology Authors: Emma Jones Elizabeth Hill Jacqueline Linehan Tamsin Nazari Adam Caulder Gemma F Codner Marie Hutchison Matthew Mackenzie Michael Farmer Thomas Coysh Michael Wiggins De Oliveira Huda Al-Doujaily Malin Sandberg Emmanuelle Vir é Thomas J Cunningham Emmanuel Source Type: research
Characterisation and prion transmission study in mice with genetic reduction of sporadic Creutzfeldt-Jakob disease risk gene Stx6
Neurobiol Dis. 2023 Nov 21:106363. doi: 10.1016/j.nbd.2023.106363. Online ahead of print.ABSTRACTSporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is thought to occur when the cellular prion protein (PrPC) spontaneously misfolds and assembles into prion fibrils, culminating in fatal neurodegeneration. In a genome-wide association study of sCJD, we recently identified risk variants in and around the gene STX6, with evidence to suggest a causal increase of STX6 expression in disease-relevant brain regions. STX6 encodes syntaxin-6, a SNARE protein primarily involved in early endosome to trans-Gol...
Source: Neurobiology of Disease - November 23, 2023 Category: Neurology Authors: Emma Jones Elizabeth Hill Jacqueline Linehan Tamsin Nazari Adam Caulder Gemma F Codner Marie Hutchison Matthew Mackenzie Michael Farmer Thomas Coysh Michael Wiggins De Oliveira Huda Al-Doujaily Malin Sandberg Emmanuelle Vir é Thomas J Cunningham Emmanuel Source Type: research
Characterisation and prion transmission study in mice with genetic reduction of sporadic Creutzfeldt-Jakob disease risk gene Stx6
Neurobiol Dis. 2023 Nov 21:106363. doi: 10.1016/j.nbd.2023.106363. Online ahead of print.ABSTRACTSporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is thought to occur when the cellular prion protein (PrPC) spontaneously misfolds and assembles into prion fibrils, culminating in fatal neurodegeneration. In a genome-wide association study of sCJD, we recently identified risk variants in and around the gene STX6, with evidence to suggest a causal increase of STX6 expression in disease-relevant brain regions. STX6 encodes syntaxin-6, a SNARE protein primarily involved in early endosome to trans-Gol...
Source: Neurobiology of Disease - November 23, 2023 Category: Neurology Authors: Emma Jones Elizabeth Hill Jacqueline Linehan Tamsin Nazari Adam Caulder Gemma F Codner Marie Hutchison Matthew Mackenzie Michael Farmer Thomas Coysh Michael Wiggins De Oliveira Huda Al-Doujaily Malin Sandberg Emmanuelle Vir é Thomas J Cunningham Emmanuel Source Type: research
Sex-specific developmental alterations in DYRK1A expression in the brain of a down syndrome mouse model
Neurobiol Dis. 2023 Nov 20:106359. doi: 10.1016/j.nbd.2023.106359. Online ahead of print.ABSTRACTAberrant neurodevelopment in Down syndrome (DS)-caused by triplication of human chromosome 21-is commonly attributed to gene dosage imbalance, linking overexpression of trisomic genes with disrupted developmental processes, with DYRK1A particularly implicated. We hypothesized that regional brain DYRK1A protein overexpression in trisomic mice varies over development in sex-specific patterns that may be distinct from Dyrk1a transcription, and reduction of Dyrk1a copy number from 3 to 2 in otherwise trisomic mice reduces DYRK1A, i...
Source: Neurobiology of Disease - November 22, 2023 Category: Neurology Authors: Laura E Hawley Megan Stringer Abigail J Deal Andrew Folz Charles R Goodlett Randall J Roper Source Type: research
External segment of the globus pallidus in health and disease: Its interactions with the striatum and subthalamic nucleus
Neurobiol Dis. 2023 Nov 20:106362. doi: 10.1016/j.nbd.2023.106362. Online ahead of print.ABSTRACTThe external segment of the globus pallidus (GPe) has long been considered a homogeneous structure that receives inputs from the striatum and sends processed information to the subthalamic nucleus, composing a relay nucleus of the indirect pathway that contributes to movement suppression. Recent methodological revolution in rodents led to the identification of two distinct cell types in the GPe with different fiber connections. The GPe may be regarded as a dynamic, complex and influential center within the basal ganglia circuit...
Source: Neurobiology of Disease - November 22, 2023 Category: Neurology Authors: Atsushi Nambu Satomi Chiken Source Type: research
Cell-type brain-region specific changes in prefrontal cortex of a mouse model of alcohol dependence
Neurobiol Dis. 2023 Nov 20:106361. doi: 10.1016/j.nbd.2023.106361. Online ahead of print.ABSTRACTThe prefrontal cortex is a crucial regulator of alcohol drinking, and dependence, and other behavioral phenotypes associated with AUD. Comprehensive identification of cell-type specific transcriptomic changes in alcohol dependence will improve our understanding of mechanisms underlying the excessive alcohol use associated with alcohol dependence and will refine targets for therapeutic development. We performed single nucleus RNA sequencing (snRNA-seq) and Visium spatial gene expression profiling on the medial prefrontal cortex ...
Source: Neurobiology of Disease - November 22, 2023 Category: Neurology Authors: Nihal A Salem Lawrence Manzano Michael W Keist Olga Ponomareva Amanda J Roberts Marisa Roberto R Dayne Mayfield Source Type: research
Activin A targets extrasynaptic NMDA receptors to ameliorate neuronal and behavioral deficits in a mouse model of Huntington disease
Neurobiol Dis. 2023 Nov 20;189:106360. doi: 10.1016/j.nbd.2023.106360. Online ahead of print.ABSTRACTCortical-striatal synaptic dysfunction, including enhanced toxic signaling by extrasynaptic N-methyl-d-aspartate receptors (eNMDARs), precedes neurodegeneration in Huntington disease (HD). A previous study showed Activin A, whose transcription is upregulated by calcium influx via synaptic NMDARs, suppresses eNMDAR signaling. Therefore, we examined the role of Activin A in the YAC128 HD mouse model, comparing it to wild-type controls. We found decreased Activin A secretion in YAC128 cortical-striatal co-cultures, while Activ...
Source: Neurobiology of Disease - November 22, 2023 Category: Neurology Authors: Wissam B Nassrallah Daniel Ramandi Judy Cheng Jean Oh James Mackay Marja D Sepers David Lau Hilmar Bading Lynn A Raymond Source Type: research
Sex-specific developmental alterations in DYRK1A expression in the brain of a down syndrome mouse model
Neurobiol Dis. 2023 Nov 20:106359. doi: 10.1016/j.nbd.2023.106359. Online ahead of print.ABSTRACTAberrant neurodevelopment in Down syndrome (DS)-caused by triplication of human chromosome 21-is commonly attributed to gene dosage imbalance, linking overexpression of trisomic genes with disrupted developmental processes, with DYRK1A particularly implicated. We hypothesized that regional brain DYRK1A protein overexpression in trisomic mice varies over development in sex-specific patterns that may be distinct from Dyrk1a transcription, and reduction of Dyrk1a copy number from 3 to 2 in otherwise trisomic mice reduces DYRK1A, i...
Source: Neurobiology of Disease - November 22, 2023 Category: Neurology Authors: Laura E Hawley Megan Stringer Abigail J Deal Andrew Folz Charles R Goodlett Randall J Roper Source Type: research
