Effect of low endogenous brain-derived neurotrophic factor levels on striatal dopamine dynamics

EFFECT OF LOW ENDOGENOUS BRAIN-DERIVED NEUROTROPHIC FACTORLEVELS ON STRIATAL DOPAMINE DYNAMICSbyFRANCIS KABUI MAINADecember 2011Advisor: Dr. Tiffany A. MathewsMajor: Chemistry (Analytical)Degree: Doctor of PhilosophyMany neurological diseases and disorders are a result of alterations withneurotransmitters, neuromodulators, and/or proteins. Specifically, one protein that hasbeen linked to numerous neurological diseases and disorders such as Parkinson’sdisease, Huntington’s disease, addiction, attention deficit hyperactivity disorder (ADHD),and depression is brain-derived neurotrophic factor (BDNF). As a trophic factor, BDNFrole is to assist in the growth, survival, and differentiation of neurons. However, there isincreasing evidence that BDNF may mediate neurotransmitter dynamics. Our goalswere to understand how endogenous BDNF levels and aging modulate the dopamine(DA) dynamics in the mouse striatum. Two complementary neurochemical techniques,slice (in vitro) fast scan cyclic voltammetry (FSCV) and in vivo microdialysis were used to characterize striatal DA dynamics in wildtype and BDNF heterozygous mutant(BDNF) mice.Overall, our findings highlight that (1) we were able to develop a reliable FSCVassay to characterize DA release-regulating D2 and D3 autoreceptors functionality inthe striatum of wildtype (C57BL/6) mice, (2) BDNF mice appear to be