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The Journal of Neuroscience, January 1, 2000, 20(1):274-282
Evidence that Brain-Derived Neurotrophic Factor from Presynaptic Nerve Terminals Regulates the Phenotype of Calbindin-Containing Neurons in the Lateral Septum
James P. Fawcett, Mario A. Alonso-Vanegas, Stephen J. Morris, Freda D. Miller, Abbas F. Sadikot, and Richard A. Murphy Center for Neuronal Survival and Division of Neurosurgery, and Montreal Neurological Institute and the Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3A 2B4
Brain-derived neurotrophic factor (BDNF) is transported anterogradely in neurons of the CNS and can be released by activity-dependent mechanisms to regulate synaptic plasticity. However, few neural networks have been identified in which the production, transport, and effects of BDNF on postsynaptic neurons can be analyzed in detail. In this study, we have identified such a network. BDNF has been colocalized by immunocytochemistry with tyrosine hydroxylase (TH) in nerve fibers and nerve terminals within the lateral septum of rats. BDNF-containing nerve fibers terminate on a population of calbindin-containing neurons in lateral septum that contain TrkB, the high-affinity receptor for BDNF. Overexpression of BDNF in noradrenergic neurons increased levels of calbindin in septum, as well as in whole-brain lysates. Septal levels of calbindin and BDNF partially decreased after unilateral lesions of the medial forebrain bundle (MFB), induced with 6-hydroxydopamine, a treatment that abolished TH staining. These data suggest that BDNF is anterogradely transported within the MFB in catecholaminergic neurons arising from brainstem nuclei. To determine whether BDNF affects the production of calbindin in lateral septal neurons directly, we tested the effects of BDNF on cultures of septal neurons from embryonic day 16-17 rats. BDNF promoted the expression of calbindin, as well as the arborization of calbindin-containing neurons, but BDNF had no effect on cell division or survival. Together, these results suggest that BDNF, anterogradely transported in catecholaminergic neurons, regulates calbindin expression within the lateral septum.
Key words: BDNF; calbindin; catecholaminergic neurons; septum; anterograde transport; TrkB
Copyright © 2000 Society for Neuroscience 0270-6474/0/201274-09$05.00/0
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