The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity.

TitleThe perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity.
Publication TypeJournal Article
Year of Publication2015
AuthorsYin F, Yao J, Sancheti H, Feng T, Melcangi RC, Morgan TE, Finch CE, Pike CJ, Mack WJ, Cadenas E, Brinton RD
JournalNeurobiol Aging
Date Published2015 Jul
KeywordsAging, Alzheimer Disease, AMP-Activated Protein Kinases, Amyloid beta-Peptides, Animals, Brain, Energy Metabolism, Fatty Acids, Female, Gene Expression, Gene Expression Regulation, Developmental, Glucose, Insulin-Like Growth Factor I, Lipid Metabolism, Long-Term Potentiation, Mitochondria, Models, Animal, Neuronal Plasticity, Perimenopause, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Rats, Sprague-Dawley, Transcription Factors

The perimenopause is an aging transition unique to the female that leads to reproductive senescence which can be characterized by multiple neurological symptoms. To better understand potential underlying mechanisms of neurological symptoms of perimenopause, the present study determined genomic, biochemical, brain metabolic, and electrophysiological transformations that occur during this transition using a rat model recapitulating fundamental characteristics of the human perimenopause. Gene expression analyses indicated two distinct aging programs: chronological and endocrine. A critical period emerged during the endocrine transition from regular to irregular cycling characterized by decline in bioenergetic gene expression, confirmed by deficits in fluorodeoxyglucose-positron emission tomography (FDG-PET) brain metabolism, mitochondrial function, and long-term potentiation. Bioinformatic analysis predicted insulin/insulin-like growth factor 1 and adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK/PGC1α) signaling pathways as upstream regulators. Onset of acyclicity was accompanied by a rise in genes required for fatty acid metabolism, inflammation, and mitochondrial function. Subsequent chronological aging resulted in decline of genes required for mitochondrial function and β-amyloid degradation. Emergence of glucose hypometabolism and impaired synaptic function in brain provide plausible mechanisms of neurological symptoms of perimenopause and may be predictive of later-life vulnerability to hypometabolic conditions such as Alzheimer's.

Alternate JournalNeurobiol. Aging
PubMed ID25921624
PubMed Central IDPMC4416218
Grant ListP01 AG026572 / AG / NIA NIH HHS / United States
P01AG026572 / AG / NIA NIH HHS / United States
Faculty Member Reference: 
Roberta Diaz Brinton, Ph.D
Fei Yin, Ph.D.