Name and Degree(s)

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BIRCWH PROJECT           

Mona Buhusi, M.D., Ph.D.  

Estrogen - BDNF Interactions in the Aging Female Brain

ABSTRACT: Cognitive decline, either during normal aging or accompanying neurodegenerative diseases, represents a major health problem in aging populations. In aging women changes in levels of sex hormones play an important role in postmenopausal cognitive decline and increase the risks of neurodegenerative disease, including Alzheimer’s disease.
Estrogen and neurotrophins act synergistically to regulate critically important processes in developing and adult brains, including neuronal survival, synaptogenesis and synaptic plasticity, and to enhance cognitive performance, but the manner in which they interact is less understood.
By using a multilevel approach (molecular, cellular, behavioral) this project will analyze the interaction between estrogen and BDNF in the female mouse hippocampus and its particularities in young and aged female mice. First, we will correlate memory performance with estrogen and BDNF levels in young and aged female mice. Second, we will evaluate what part does estrogen-induced BDNF secretion play in the beneficial effect of estrogen on hippocampal neurons and memory. Third, we will investigate which of the estrogen receptors (α or β) is involved in BDNF secretion in the hippocampus. Together, these studies will increase our understanding of the molecular mechanisms of estrogen effects in the nervous system and of the neuronal dysfunction underlying memory deficits in aged females, and may provide new targets for preventive interventions and therapy.

Matthew Feltenstein, Ph.D.

Role of Sex, Estrous Cycle and Ovarian Hormones in Cocaine-Seeking Behavior

ABSTRACT: Relapse to drug abuse following abstinence is a significant impediment in the treatment of drug dependence.  Although various factors (stress, conditioned cues, drugs) that contribute to relapse have been studied in males, the impact in females has been less explored.  We have recently shown sex differences for conditioned cue-induced, stress and drug-primed reinstatement of cocaine-seeking in an animal model of relapse, whereby males are more susceptible to cues and females more responsive to stress and cocaine injections.  Moreover, the differences seen in females are closely linked to the estrus phase of the estrous cycle.  Building on these previous studies, this project will provide a comprehensive approach to nicotine-seeking behavior by examining sex and estrous cycle dependent differences in stress, cue, and drug-primed reinstatement of nicotine-seeking.

Crystal Flynn Longmire, Ph.D.   

Gender Differences in Cognitive Decline

ABSTRACT: Little is known about cognitive decline and the progression of Alzheimer’s disease (AD) among women. The progression of AD among women is an important health issue to study because the risk of AD is somewhat higher in women.  Proportionally, since women often represent the majority in older age groups they are often the majority of the AD cases.  The South Carolina Alzheimer’s Disease Registry confirms this trend in South Carolina (SC), where the women represent 66% of the AD and related dementia cases.  The primary research question posed by this research is whether or not there are differences in rates of cognitive decline between middle-aged to older women and men among normal, mildly cognitively impaired, and AD patients in SC and national samples.  The project includes tests of four domains of cognitive function: memory, language, attention/executive function, and processing speed and employs secondary data analysis to observe which cognitive test and domain scores decline over the study period and if their rates of decline differ by gender.

Karen Hartwell, M.D.

Gender Differences in Response to NRT and Denicotinized Cigarette-Facilitated Extinction

ABSTRACT: Women smokers are less responsive to nicotine replacement therapy (NRT) and more responsive to environmental cues associated with smoking behavior.  This pilot study is designed to increase understanding of the neural circuitry underlying these differences. In the proposed study, adult male and female (10 per group) treatment-seeking nicotine-dependent individuals will participate in functional magnetic resonance imaging (fMRI) with the presentation of smoking-related cues under three conditions during a seven day period: baseline, after NRT, and after denicotinized cigarette facilitated-extinction.