Premium
P3‐135: BRAIN IMAGING, BEHAVIORAL EVALUATIONS, BIOCHEMICAL ANALYSIS, AND PROTEOMES PROFILING IN AGED RATS
Author(s) -
Hamezah Hamizah Shahirah,
Durani Lina Wati,
Ibrahim Nor Faeizah,
Yanagisawa Daijiro,
Kato Tomoko,
Makpol Suzana,
Damanhuri Hanafi Ahmad,
Tooyama Ikuo
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.1492
Subject(s) - striatum , prefrontal cortex , hippocampus , malondialdehyde , oxidative stress , neuroscience , morris water navigation task , glutathione peroxidase , psychology , medicine , chemistry , cognition , superoxide dismutase , dopamine
pathways among biological groups by summarizing all pairwise GSEA results. Hierarchical clustering was applied to identify significant interactions between emerged pathways. Results: PCA revealed that rats undergoing perimenopause exhibit substantially higher variances in overall hippocampal gene expression relative to other groups, supporting the perimenopausal brain being in an unstable transition state. While PCA and DEG analyses of hippocampal RNA suggest significant difference among age-matched pre-/peri-/menopause brains, the difference in the hypothalamus was minor, suggesting hippocampus but not hypothalamus as a major brain site affected by endocrine aging. GSEA further revealed alterations in bioenergetic-, inflammatory-, and cell proliferation pathways during the transition featured by declining bioenergetic genes and low-grade activation of immune pathways. Moreover, nuclear(nDNA) or mitochondrial DNA (mtDNA)-encoded bioenergetic genes are differentially regulated by chronologicaland endocrine aging: mtDNA genes correlated closely with chronological aging while nDNA-encoded counterparts were largely endocrine dependent. Lastly, the strong correlation between bioenergetic pathway with genes involved in AD and other neurodegenerative disorders linked bioenergetic deficits to neurodegeneration and elevated AD vulnerability. Conclusions: Our findings suggest that hippocampal gene expression during perimenopause is a transition state characterized by perturbations to primarily bioenergeticand inflammatory pathways, which could contribute to increased AD risk in women. This study provides novel mechanistic insights into the impact of perimenopausal transition on brain function, which could have implications for identifying phenotypes of AD risk for earliest detection in aging females.