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

NEUROBIOLOGY OF AGING

卷:36

Article

Yin, Fei¹  Yao, Jia¹  Sancheti, Harsh¹  Feng, Tao²  Melcangi, Roberto C.³  Morgan, Todd E.⁴  Finch, Caleb E.⁴  Pike, Christian J.⁴  Mack, Wendy J.²  Cadenas, Enrique¹  Brinton, Roberta D.^1,5 

[1] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA

[2] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA

[3] Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy

[4] Univ So Calif, Davis Sch Gerontol, Los Angeles, CA 90089 USA

[5] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90089 USA

关键词: Perimenopause;    Female brain aging;    Glucose metabolism;    Mitochondria;    Synaptic plasticity;    Hypometabolism;    Fatty acid metabolism;    Long-term potentiation;   

DOI  :  10.1016/j.neurobiolaging.2015.03.013

来源: Elsevier

【 摘 要 】

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 fluorodeoxyglucoseepositron 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/PGC1 alpha) 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 beta-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. (C) 2015 Elsevier Inc. All rights reserved.

【 授权许可】

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