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Journal of Neuroscience, Vol 13, 3818-3826, Copyright © 1993 by Society for Neuroscience
Cholinergic regulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) but not neurotrophin-3 (NT-3) mRNA levels in the developing rat hippocampus
M da Penha Berzaghi, J Cooper, E Castren, F Zafra, M Sofroniew, H Thoenen and D Lindholm
Department of Neurochemistry, Max Planck Institute for Psychiatry, Planegg Martinsried, Germany.
In previous experiments it has been demonstrated that the synthesis of BDNF
(brain-derived neurotrophic factor) and NGF in neurons of the hippocampus
is regulated by neuronal activity. The glutamate system is predominantly
responsible for upregulation and the GABAergic system for downregulation
both in vitro and in vivo (Zafra et al., 1990, 1991). The aim of the
present study is to examine the extent to which the cholinergic system is
also involved in the regulation of NGF and BDNF mRNA and whether the
regulatory contribution of the cholinergic system changes during
development. Partial transection of the fimbria fornix bundle in the second
postnatal week resulted in a reduction of BDNF and NGF mRNA levels in the
hippocampus, suggesting that septal cholinergic input is involved in the
regulation of hippocampal BDNF and NGF mRNA levels. Because the fimbria
fornix bundle also contains fibers other than cholinergic ones, we further
evaluated the importance of the cholinergic influence by injecting
pilocarpine, a muscarinic agonist. Pilocarpine markedly increased
hippocampal BDNF and NGF mRNA levels in both early postnatal and adult
rats. In situ hybridization experiments demonstrated that pilocarpine led
to an increase in BDNF expression in the CA1-CA4 regions of the hippocampus
and in the dentate gyrus. However, pilocarpine increased NGF mRNA only in
those neurons of the dentate gyrus and CA1-CA4 regions that also expressed
NGF mRNA in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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