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• W3194864246 abstract "Down syndrome (DS) is the primary genetic cause of intellectual disability (ID), which is due to the triplication of human chromosome 21 (HSA21). In addition to ID, HSA21 trisomy results in a number of neurological and physiological pathologies in individuals with DS, including progressive cognitive dysfunction and learning and memory deficits which worsen with age. Further exacerbating neurological dysfunction associated with DS is the concomitant basal forebrain cholinergic neuron (BFCN) degeneration and onset of Alzheimer's disease (AD) pathology in early mid-life. Recent single population RNA sequencing (RNA-seq) analysis in the Ts65Dn mouse model of DS, specifically the medial septal cholinergic neurons of the basal forebrain (BF), revealed the mitochondrial oxidative phosphorylation pathway was significantly impacted, with a large subset of genes within this pathway being downregulated. We further queried oxidative phosphorylation pathway dysregulation in Ts65Dn mice by examining genes and encoded proteins within brain regions comprising the basocortical system at the start of BFCN degeneration (6 months of age). In select Ts65Dn mice we demonstrate significant deficits in gene and/or encoded protein levels of Complex I-V of the mitochondrial oxidative phosphorylation pathway in the BF. In the frontal cortex (Fr Ctx) these complexes had concomitant alterations in select gene expression but not of the proteins queried from Complex I-V, suggesting that defects at this time point in the BF are more severe and occur prior to cortical dysfunction within the basocortical circuit. We propose dysregulation within mitochondrial oxidative phosphorylation complexes is an early marker of cognitive decline onset and specifically linked to BFCN degeneration that may propagate pathology throughout cortical memory and executive function circuits in DS and AD." @default.
• W3194864246 created "2021-08-30" @default.
• W3194864246 creator A5047993013 @default.
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• W3194864246 creator A5077428900 @default.
• W3194864246 date "2021-08-19" @default.
• W3194864246 modified "2023-09-27" @default.
• W3194864246 title "Oxidative Phosphorylation Is Dysregulated Within the Basocortical Circuit in a 6-month old Mouse Model of Down Syndrome and Alzheimer’s Disease" @default.
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• W3194864246 doi "https://doi.org/10.3389/fnagi.2021.707950" @default.
• W3194864246 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8417045" @default.
• W3194864246 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34489678" @default.
• W3194864246 hasPublicationYear "2021" @default.
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