Current Research Interests

Serptonin and BDNF Recent research has provided insight about the relationship between the serotoninneurotransmitter system and brain-derived neurotrophic factor (BDNF). Serotonin has been proposed to stimulate the expression of BDNF, while BDNF enhances the growth and survival of serotonergic neurons. Also, inhibition of the serotonin transporter in response to antidepressant drugs has been shown to alter neuronal plasticity by regulating the expression of critical genes including BDNF and this has been linked the therapeutic mechanism of action.. Studies by our group on BDNF+/- mice, using zero-net flux microdialysis, demonstrated that changes in extracellular serotonin concentrations are only observable well after induction of ageaccelerated degeneration of serotonergic neurons. Based on this, we hypothesize that alterations in serotonin release and reuptake resulting from constitutive reductions in BDNF occurring prior to the emergence of changes in behavior and thereby, contributing to these changes, might only be observed using an analytical method like FCV. Hippocampal Neurogenesis The serotonin transporter (SERT, 5-HTT, SLC6A4) is a key focus of investigation because it is the primary molecular target for the serotonin-selective reuptake inhibitors -- the most widely prescribed class of antidepressant and anti-anxiety medications. Preclinical studies have demonstrated that long-term antidepressant treatment increases the generation of new neurons in the hippocampus. Furthermore, increases in adult hippocampal neurogenesis have been shown to play a critical role in antidepressant-mediated reductions in anxiety and stress responsiveness. A commonly occurring functional polymorphism in the promoter region of the primate serotonin transporter gene has also received considerable attention due to its association with increased anxiety-related traits and susceptibility to depression. Together these data suggest that the effects of reduced serotonin transporter function are contextually dependent such that constitutive versus adult-mediated inhibition of serotonin reuptake results in opposing effects on anxiety-related behavior. We are carrying out studies in the rhesus dentate gyrus of hippocampus because rhesus monkeys express a native serotonin transporter gene-linked promoter polymorphism (rh5HTTLPR) that is orthologus to the human SERT gene variant. Recent Publications 1. The neurotoxin 2'-NH2-MPTP degenerates serotonin axons and evokes increases in hippocampal BDNF. B. A. Luellen, M. E. Szapacs, C. K. Materese and A. M. Andrews, Neuropharmacology, 50:297-308 (2006) (ABSTRACT or PDF). 2. Radical-induced degradation of liposome-encapsulated microtubules as a model of axonal damage due to oxidative stress. A. E. Counterman, T. G. D'Onofrio, A. M. Andrews and P. S. Weiss, Proceedings of the National Academy of Sciences, USA, 103:5262-5266 (2006) (ABSTRACT or PDF). 3. Reduced BDNF is associated with a loss of serotonergic innervation in the hippocampus of aging mice. B. A. Luellen, L. E. Bianco, L. M. Schneider and A. M. Andrews, Genes, Brain and Behavior, (Dec 2006) (ABSTRACT or PDF). back	Techniques Used
	Behavioral Tests
		Elevated Plus Maze
		Free Choice Exploraion
		Lashley Maze
	Immunocytochemistry
	Quantitative RT-PCR
	Electroanalyticl Methods
		Fast Cylic Volatmmetry

BDNF and Neurogenesis

Graduate Programs

Other Links