Title | Lifelong chronic psychosocial stress induces a proteomic signature of Alzheimer's disease in wildtype mice. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Lyons CE, Zhou X, Razzoli M, Chen M, Xia W, Ashe K, Zhang B, Bartolomucci A |
Journal | Eur J Neurosci |
Date Published | 2021 May 28 |
ISSN | 1460-9568 |
Abstract | Late onset, sporadic Alzheimer's disease (AD) accounts for the vast majority of cases. Unlike familial AD, the factors that drive the onset of sporadic AD are poorly understood, although aging and stress play a role. The early onset/severity of neuropathology observed in most genetic mouse models of AD hampers the study of the role of aging and environmental factors; thus alternate strategies are necessary to understand the contributions of these factors to sporadic AD. We demonstrate that mice acquiring a low social status (subordinate) in a lifelong chronic psychosocial stress (CPS) model, accrue widespread proteomic changes in the frontal/temporal cortex during aging. To better understand the significance of these stress-induced changes, we compared the differentially expressed proteins (DEPs) of subordinate mice to those of patients at varying stages of dementia. Sixteen and fifteen DEPs upregulated in subordinate mice were also upregulated in patients with mild cognitive impairment (MCI) and AD, respectively. Six of those upregulated proteins (CPE, ERC2, GRIN2B, SLC6A1, SYN1, WFS1) were shared by subordinate mice and patients with MCI or AD. Finally, comparison with a spatially detailed transcriptomic database revealed that the superior frontal gyrus and hippocampus had the greatest overlap between mice subjected to lifelong CPS and AD patients. Overall, most of the overlapping proteins were functionally associated with enhanced NMDA receptor mediated glutamatergic signaling, an excitotoxicity mechanism known to affect neurodegeneration. These findings support the association between stress and AD progression and provide valuable insight into potential early biomarkers and protein mediators of this relationship. |
DOI | 10.1111/ejn.15329 |
Pubmed Link | https://www.ncbi.nlm.nih.gov/pubmed/34048087?dopt=Abstract |
page_expo | Internal |
Alternate Journal | Eur J Neurosci |
PubMed ID | 34048087 |
Grant List | 18.4 / / MN Partnership for Biotechnology and Molecular Genomic / T32AG029796 / / MN Partnership for Biotechnology and Molecular Genomic / R01AG046170 / AG / NIA NIH HHS / United States RF1AG057440 / AG / NIA NIH HHS / United States R01AG057907 / AG / NIA NIH HHS / United States U01AG052411 / AG / NIA NIH HHS / United States R03DE026814 / DE / NIDCR NIH HHS / United States R01DK117504 / DK / NIDDK NIH HHS / United States R01DK118243 / DK / NIDDK NIH HHS / United States U01AI111598 / / National Institute of Allergy and Infectious Diseases / |
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