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

Autor: Tao Feng, Todd E. Morgan, Enrique Cadenas, Harsh Sancheti, Wendy J. Mack, Fei Yin, Jia Yao, Roberta Diaz Brinton, Christian J. Pike, Caleb E. Finch, Roberto Cosimo Melcangi
Rok vydání: 2015
Předmět:
Aging
medicine.medical_specialty
Long-Term Potentiation
Gene Expression
AMP-Activated Protein Kinases
Mitochondrion
Biology
Article
Rats
Sprague-Dawley
Reproductive senescence
AMP-activated protein kinase
Alzheimer Disease
Internal medicine
Neuroplasticity
medicine
Animals
Insulin-Like Growth Factor I
Amyloid beta-Peptides
Neuronal Plasticity
Bioenergetic systems
General Neuroscience
Fatty Acids
Brain
Gene Expression Regulation
Developmental
Long-term potentiation
Lipid Metabolism
medicine.disease
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Mitochondria
Perimenopause
Glucose
Endocrinology
Models
Animal
Synaptic plasticity
biology.protein
Female
Neurology (clinical)
Geriatrics and Gerontology
Alzheimer's disease
Energy Metabolism
Neuroscience
Transcription Factors
Developmental Biology
Zdroj: Neurobiology of Aging. 36:2282-2295
ISSN: 0197-4580
DOI: 10.1016/j.neurobiolaging.2015.03.013
Popis: 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.
Databáze: OpenAIRE
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