Project Title: Aging and Estrogenic Control of the Bioenergetic System in Brain * PI Name: BRINTON, ROBERTA DIAZ, Professor in the Department of Pharmacology, COM, Director of the Center for Innovation in Brain Science
For estrogen to function as master regulator of the bioenergetic system in the female brain, estrogen must be integrating nuclear and mitochondrial genomic responses. Further, from a systems level perspective, it would be necessary for estrogen to also regulate cytoplasmic signaling mechanisms for real time feedback on the functional outcomes of nuclear and mitochondrial gene transcription. The fundamental issues to be investigated are the mechanisms whereby estrogen integrates bioenergetic responses across two genomic compartments while simultaneously monitoring energetic demand and performance in real time. Estrogenic control of the bioenergetic system of the brain and the dismantling thereof has basic, translational and clinical significance.
From a discovery perspective the proposed program of research is unique in exploring the mechanisms underlying estrogenic integration of nuclear and mitochondrial gene expression and the real time feedback mechanisms that control the bioenergetic system of the brain. Further, the process by which this control system is dismantled in the aging female brain is uncharted territory of high significance for understanding bioenergetic aging in brain. Translationally, determining the mechanisms underlying the systematic dismantling of estrogenic integration of bioenergetic compartments in brain has the potential to detect therapeutic targets to sustain bioenergetic function in the aging female brain. Clinically, the aging transition of menopause, unique to the female, is a process that dismantles both reproductive ability and potentially bioenergetic capacity in brain. This is particularly relevant to age-related neurological conditions associated with deficits in glucose hypometabolism such as Alzheimer's, depression and multiple sclerosis which have greater prevalence in postmenopausal women.
PUBLIC HEALTH RELEVANCE: In the US and elsewhere, the predominant face of aging will be female as aged women will outnumber men by two to one. Understanding how estrogen, the predominant feminizing hormone, acts to promote and sustain the energy producing system of the brain is critical to revealing changes that occur in the aging female brain that can increase the risk of age-associated neurodegenerative diseases in postmenopausal women such as Alzheimer's, depression and multiple sclerosis.
Contact: Kathy Glockner, firstname.lastname@example.org