PMID- 10739636 OWN - NLM STAT- MEDLINE DCOM- 20000523 LR - 20131121 IS - 0014-4886 (Print) IS - 0014-4886 (Linking) VI - 162 IP - 2 DP - 2000 Apr TI - BDNF is needed for postnatal maturation of basal forebrain and neostriatum cholinergic neurons in vivo. PG - 297-310 AB - Neurotrophins regulate survival, neurite outgrowth, and phenotypic maturation of developing neurons. Brain-derived neurotrophic factor (BDNF) can promote the survival of developing cholinergic forebrain neurons in vitro and reduce their degeneration following injury in adult rats. We investigated the role of endogenous BDNF during postnatal development of these cholinergic neurons by analyzing homozygous BDNF-deficient (-/-) mice and their littermates (+/+, +/-). At P6, the number of choline acetyltransferase- (ChAT) positive neurons in the medial septum was approximately 23% lower in BDNF-/- mice, although their brain and body weight was normal. At P15, control (+/+) littermates had approximately 45% more and approximately 45% larger ChAT-positive neurons and a much denser cholinergic hippocampal innervation than at P6, indicative of maturation of the septohippocampal system. In BDNF-/- mice, the number, size, and ChAT-immunostaining intensity of the cholinergic neurons remained the same between P6 and P15 (few mice survive longer). BDNF-/- mice had about three times more TUNEL-labeled (a marker of apoptosis) cells in the medial septum at P6, consistent with (but not proof of) the possibility that the cholinergic neurons were dying. The cholinergic hippocampal innervation in BDNF-/- mice expanded to a lesser extent than in controls and had reduced levels of acetylcholinesterase staining at P15. The developmental deficits were largely similar in the neostriatum of BDNF-/- mice. These findings suggest that BDNF is critical for postnatal development and maturation of cholinergic forebrain neurons. CI - Copyright 2000 Academic Press. FAU - Ward, N L AU - Ward NL AD - Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada. FAU - Hagg, T AU - Hagg T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 2.3.1.6 (Choline O-Acetyltransferase) RN - N9YNS0M02X (Acetylcholine) SB - IM MH - Acetylcholine/metabolism MH - Animals MH - Apoptosis MH - Body Weight MH - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology MH - Cell Count/drug effects MH - Choline O-Acetyltransferase/metabolism MH - Heterozygote MH - Hippocampus/cytology/drug effects/enzymology/growth & development MH - Homozygote MH - In Situ Nick-End Labeling MH - Mice MH - Mice, Knockout MH - Neostriatum/cytology/drug effects/enzymology/*growth & development MH - Nerve Fibers/drug effects/enzymology MH - Neurons/*cytology/drug effects/*enzymology MH - Septum of Brain/cytology/drug effects/enzymology/*growth & development EDAT- 2000/03/31 09:00 MHDA- 2000/06/08 09:00 CRDT- 2000/03/31 09:00 PHST- 2000/03/31 09:00 [pubmed] PHST- 2000/06/08 09:00 [medline] PHST- 2000/03/31 09:00 [entrez] AID - S0014-4886(99)97346-6 [pii] AID - 10.1006/exnr.1999.7346 [doi] PST - ppublish SO - Exp Neurol. 2000 Apr;162(2):297-310. doi: 10.1006/exnr.1999.7346.