The mission of our Perimenopause in Brain Aging and Alzheimer's Disease Program Project (P3) is to discover the biological changes that occur in the brain during the perimenopausal transition which can result in phenotypes predictive of risk for development of Alzheimer's pathology. We seek to identify the mechanisms by which these changes occur, and translate these discoveries to determine the optimal timing and strategies for preventing conversion to the perimenopausal at-risk phenotype. To achieve our mission, we will determine the perimenopausal phenotypes associated with different cycle transition states;delineate the mechanistic pathways involved in cJevelopment of these phenotypes;and assess the impact of ovarian hormone and high-fat diet induced obesity (DIO) on expression of Alzheimer's disease biomarkers. The mission of Animal Core (Core B) is to ensure the success ofthe Perimenopause Program Project through provision of animals as neecled to Projects 1-3. To achieve its mission. Animal Core will develop rodent models of perimenopause and menopause;maintain and track animals from acquisition or birth, though determination of cycling status, study enrollment, experimental manipulation, to fissue collection across the entire Perimenopause Program Project;and obtain tissue samples for storage and genetic analyses by Analytic Core.

Public Health Relevance

(See Instructions): The complexity of the perimenopausal process has been a major barrier to both basic and clinical research of this aging transition in women. Development of rodent models ofthe human perimenopause is critical to advancing knowledge ofthe effects ofthe perimenopause on the brain, identifying phenotypes at risk for age-associated neurological diseases, and developing strategies that promote healthy neurological aging in women to prevent age-associated diseases such as Alzheimer's.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAG1-ZIJ-8)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Southern California
Los Angeles
United States
Zip Code
Rettberg, Jamaica R; Yao, Jia; Brinton, Roberta Diaz (2014) Estrogen: a master regulator of bioenergetic systems in the brain and body. Front Neuroendocrinol 35:8-30
Finch, Caleb E; Beltrán-Sánchez, Hiram; Crimmins, Eileen M (2014) Uneven futures of human lifespans: reckonings from Gompertz mortality rates, climate change, and air pollution. Gerontology 60:183-8
Yin, Fei; Boveris, Alberto; Cadenas, Enrique (2014) Mitochondrial energy metabolism and redox signaling in brain aging and neurodegeneration. Antioxid Redox Signal 20:353-71
Finch, Caleb E; Tower, John (2014) Sex-specific aging in flies, worms, and missing great-granddads. Cell 156:398-9
Chang, Allen H K; Sancheti, Harsh; Garcia, Jerome et al. (2014) Respiratory substrates regulate S-nitrosylation of mitochondrial proteins through a thiol-dependent pathway. Chem Res Toxicol 27:794-804
Finch, Caleb E (2014) The menopause and aging, a comparative perspective. J Steroid Biochem Mol Biol 142:132-41
Sancheti, Harsh; Kanamori, Keiko; Patil, Ishan et al. (2014) Reversal of metabolic deficits by lipoic acid in a triple transgenic mouse model of Alzheimer's disease: a 13C NMR study. J Cereb Blood Flow Metab 34:288-96
Jayaraman, Anusha; Pike, Christian J (2014) Differential effects of synthetic progestagens on neuron survival and estrogen neuroprotection in cultured neurons. Mol Cell Endocrinol 384:52-60
Yin, Fei; Jiang, Tianyi; Cadenas, Enrique (2013) Metabolic triad in brain aging: mitochondria, insulin/IGF-1 signalling and JNK signalling. Biochem Soc Trans 41:101-5
Bali, N; Arimoto, J M; Morgan, T E et al. (2013) Progesterone antagonism of neurite outgrowth depends on microglial activation via Pgrmc1/S2R. Endocrinology 154:2468-80

Showing the most recent 10 out of 54 publications