Maturation but not survival of dopaminergic nigrostriatal neurons is affected in developing and aging BDNF-deficient mice

Abstract

Brain-derived neurotrophic factor (BDNF) promotes survival of injured dopaminergic nigrostriatal neurons of the adult rodent substantia nigra pars compacta, as well their development in vitro. BDNF deficiency may play a role in Parkinson's disease, as the surviving dopaminergic nigrostriatal neurons have reduced levels of BDNF, and a BDNF gene polymorphism is present in a subpopulation of patients. Here, we investigated whether a lack of BDNF in early postnatal BDNF-/- mice or a chronic 50% reduction in BDNF levels in aging BDNF+/- mice would affect the survival of the dopaminergic nigrostriatal neurons. In general terms, BDNF-/- and BDNF+/- mice had morphologically and quantitatively normal nigrostriatal neurons at any time between postnatal day 14 (P14) and 18 months, when compared to their wild-type littermates. BDNF-/- mice (P14 and P21 only) had fewer dopaminergic dendrites in the substantia nigra, suggesting that BDNF plays a role in phenotypic maturation, but not in neuronal birth or survival. BDNF-/- mice also had aberrant tyrosine hydroxylase (TH) positive cell bodies in the pars reticulata. During adulthood and aging, BDNF+/- mice performed equally well as their wild-type littermates in tests of motor coordination, and both showed aging-related decreases in the size of the dopaminergic neurons as well as in motor coordination. These results suggest that chronic deficits in BDNF alone do not affect survival or function of dopaminergic nigrostriatal neurons during aging or potentially even in Parkinson's disease.