Sex hormone influences on brain and behavior across lifespan

Neuroplasticity cell signaling pathways in healthy and disease states

Dr. Rebecca Cunningham Lab

The Cunningham lab is focused on the neurobiology of steroid hormones, neuropeptides, and oxidative stress mediated mechanisms in order to examine sex differences in neurodegenerative diseases (e.g., Alzheimer’s disease). We are one of the first laboratories to examine how oxidative stress alters the functional outcomes of steroid hormones, such as androgens and estrogens. We found that androgens has both neuroprotective qualities and neurotoxic properties. Androgens can decrease oxidative stress if present prior to a stress. In contrast, once oxidative stress reaches a threshold, androgens can exacerbate oxidative stress generation and neuronal vulnerability (e.g., inflammation, memory impairments, and motor dysfunction). We were the first to discover the presence of a neuronal androgen receptor splice variant (AR45) complexed to NADPH oxidase (NOX), which is localized to lipid rafts in the plasma membrane and mediates androgen induced oxidative stress signaling pathways in the central nervous system. Our overall research goal has been centered on identification and knowledge of pathways modulated by sex chromosome or steroid hormones that can lead to improved health outcomes by providing a foundation for targeted therapeutic strategies and interventions.

in vitro cell culture (neurons, astrocytes), western blots, subcellular fractionation (membranes, lipid rafts in membranes, cytosol, nucleus), rtPCR, microscopy (immunohistochemistry, live cell imaging), colorimetric assays, ELISAs, multiplex ELISAs (e.g., inflammation, hormones, etc in plasma/serum and tissue), Alzet pump (subcutaneous, ventricle, brain region), telemetry implantation, microdissection of discrete brain regions, estrous cycle determination, animal surgeries (gonadectomies, stereotaxic surgeries, telemetry), rat behaviors (e.g., memory, motor, vocalizations, social, anxiety, compulsivity, reproductive, preference).