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Publication : Longitudinal characterization of behavioral, morphological and transcriptomic changes in a tauopathy mouse model.

First Author  Cao Q Year  2023
Journal  Aging (Albany NY) Volume  15
Issue  21 Pages  11697-11719
PubMed ID  37925173 Mgi Jnum  J:343127
Mgi Id  MGI:7562677 Doi  10.18632/aging.205057
Citation  Cao Q, et al. (2023) Longitudinal characterization of behavioral, morphological and transcriptomic changes in a tauopathy mouse model. Aging (Albany NY) 15(21):11697-11719
abstractText  Neurodegenerative disorders, such as Alzheimer's disease (AD), have the gradual onset of neurobiological changes preceding clinical diagnosis by decades. To elucidate how brain dysfunction proceeds in neurodegenerative disorders, we performed longitudinal characterization of behavioral, morphological, and transcriptomic changes in a tauopathy mouse model, P301S transgenic mice. P301S mice exhibited cognitive deficits as early as 3 months old, and deficits in social preference and social cognition at 5-6 months. They had a significant decrease of arborization in basal dendrites of hippocampal pyramidal neurons from 3 months and apical dendrites of PFC pyramidal neurons at 9 months. Transcriptomic analysis of genome-wide changes revealed the enrichment of synaptic gene upregulation at 3 months of age, while most of these synaptic genes were downregulated in PFC and hippocampus of P301S mice at 9 months. These time-dependent changes in gene expression may lead to progressive alterations of neuronal structure and function, resulting in the manifestation of behavioral symptoms in tauopathies.
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