Dataset Information

Mass spectrometry analysis of synaptic proteome of adult Fmr1 KO and wild-type mice.

ABSTRACT: Fragile X syndrome (FXS) is the most common monogenetic cause of inherited intellectual disability and autism in humans. One of the well-characterized molecular phenotypes of Fmr1 KO mice, a model of FXS, is increased translation of synaptic proteins. Although this upregulation stabilizes in the adulthood, abnormalities during the critical period of plasticity have long-term effects on circuit formation and synaptic properties. Using high-resolution quantitative proteomics of synaptoneurosomes isolated from the adult, developed brains of Fmr1 KO mice, we show differential abundance of proteins regulating postsynaptic receptor activity of glutamatergic synapse. This work includes proteomic dataset that was acquired and analyzed to quantify changes in the abundance of proteins in synaptoneurosomes (basal state, unstimulated and in vitro NMDA-R stimulated) isolated from Fmr1 KO mice and their wild-type littermates.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Fragile X Syndrome

SUBMITTER: Remigiusz Serwa

LAB HEAD: Magdalena Dziembowska

PROVIDER: PXD043700 | Pride | 2024-01-26

REPOSITORIES: Pride

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Publications

Impaired synaptic incorporation of AMPA receptors in a mouse model of fragile X syndrome.

Chojnacka Magdalena M Beroun Anna A Magnowska Marta M Stawikowska Aleksandra A Cysewski Dominik D Milek Jacek J Dziembowska Magdalena M Kuzniewska Bozena B

Frontiers in molecular neuroscience 20231109

Fragile X syndrome (FXS) is the most common monogenetic cause of inherited intellectual disability and autism in humans. One of the well-characterized molecular phenotypes of <i>Fmr1</i> KO mice, a model of FXS, is increased translation of synaptic proteins. Although this upregulation stabilizes in adulthood, abnormalities during the critical period of plasticity have long-term effects on circuit formation and synaptic properties. Using high-resolution quantitative proteomics of synaptoneurosome ...[more]

PMID: 38025260

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Project description:In Alzheimer's disease (AD), early deficits in learning and memory are a consequence of synaptic modification which are likely induced by toxic beta-amyloid oligomers (dAbeta). To identify molecular targets downstream of dAbeta binding we prepared synaptoneurosomes from frontal cortex of control and IAD patients, and isolated mRNAs for comparison of gene expression. This approach elevated synaptic mRNAs above the threshold necessary for expression changes to be discriminated and also reduced other cellular mRNAs. In patients with minimal cognitive impairment (MCI) termed incipient AD (IAD) global measures of cognition declined with increasing levels of dimeric beta (dAbeta). These patients also showed increased expression of neuroplasticity related genes, many encoding 3' UTR consensus sequences that regulate local translation in the synapse. One such gene, GluR2, displayed elevated mRNA and protein expression in IAD. Other neurotransmitter-related genes were also upregulated. Overexpressed genes may induce compensatory as well as negative effects on cognition and provide targets for intervention to moderate the response to dAbeta. Experiment Overall Design: Patient information Experiment Overall Design: CNS tissues were obtained from the USC Alzheimer's Disease Research Center (ADRC) Neuropathology Core, NIA AG05142. Clinical information, including neurological examination, neuropsychological testing such as cognitive assessment, family history, and medications were provided by the USC ADRC Clinical Core. The groups did not differ significantly in age or years of education. Medication histories indicated one IAD patient had used a selective serotonin uptake inhibitor. Post-mortem interval (PMI) ranged from 2 to 9 hours (mean 5.1 hrs.). The study included 8 normal controls and 6 patients with Incipient Alzheimer's Disease. Experiment Overall Design: To augment studies comparing homogenates of control to AD brains, we used synaptoneurosome preparations to enrich for synaptic mRNAs. Synaptoneurosomes were prepared from the prefrontal cortices of control and IAD patients by a simple, rapid, but gentle method using sequential mesh screens.

Dataset Information

Mass spectrometry analysis of synaptic proteome of adult Fmr1 KO and wild-type mice.

Publications

Impaired synaptic incorporation of AMPA receptors in a mouse model of fragile X syndrome.

Similar Datasets

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