Elucidating the cellular and molecular neuropharmacology of the aging brain is the focus of the Lakoski laboratory. Using multidisciplinary approaches to investigate biogenic amine receptor expression and function, both normal and pathological aging processes are being investigated in young, middle-aged and senescent small animal models. We are investigating the roles of the steroid hormones estrogen and corticosterone on serotonin receptors, their receptor-effector coupling to G-proteins and related signaling transduction cascades, including the 5-HT1A and 5-HT2A receptor subtypes, and the serotonin neurotransporter (SERT) in discrete brain regions including cortical, hippocampal and midbrain regions; radioligand binding techniques, receptor autoradiography and functional neurochemical assays are among the technical approaches used to study the impact of the circulating hormone environment on the aging serotonergic neuronal system.
Related ongoing studies are utilizing in vivo microPET image analysis techniques to elucidate SERT expression and function with respect to aging and hormone treatment. In addition, the impact of selective neurotoxic insults to the dopamine-containing neuronal system is being investigated using behavioral, neurochemical and molecular approaches to better understand how this neurotransmitter system responds and recovers from neuronal injury across the lifespan.
Our goal is to contribute new information to understand the biology of central nervous system aging, including normal and neurodegenerative processes, in neurotransmitter systems established as key components in cognitive declines, mood disorders, and stress-related disorders common in the elderly. Ultimately, our aim is to improve the quality of life with advancing age by pharmacological interventions to delay the onset of neuronal decline and/or enhance endogenous repair mechanisms of the biogenic amine neurotransmitter systems.
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