PMID- 10502251 OWN - NLM STAT- MEDLINE DCOM- 19991018 LR - 20190905 IS - 0021-9967 (Print) IS - 0021-9967 (Linking) VI - 413 IP - 3 DP - 1999 Oct 25 TI - Characterization of dopaminergic midbrain neurons in a DBH:BDNF transgenic mouse. PG - 449-62 AB - The neurotrophin brain-derived neurotrophic factor (BDNF) has been implicated in the survival and differentiation of central nervous system neurons, including dopaminergic cells in culture. To determine whether BDNF might play a role in the development of dopaminergic neurons in vivo, we used a previously characterized transgenic mouse (DBH:BDNF) that overexpresses BDNF in adrenergic and noradrenergic neurons as a result of fusion of the BDNF gene to the dopamine beta-hydroxylase (DBH) gene promoter. We quantified dopaminergic neuronal profiles at four midbrain coronal levels and compared DBH:BDNF transgenic animals with wild-type mice of the same genetic background. Analysis of sections immunostained with tyrosine hydroxylase (TH) showed that the mean number of dopaminergic neurons in the four selected midbrain sections was 52% greater (one-way analysis of variance, P < 0.0005) in transgenic mice (2,165 +/- 55 S. E.M., n = 4) than in control mice (1,428 +/- 71 S.E.M., n = 4). The increase in dopaminergic neuron profile count in DBH:BDNF transgenic animals was confirmed by analysis of the pars compacta of the substantia nigra on Nissl-stained sections. Surface area of the reference region of interest containing TH-immunoreactive neurons was similar in transgenic and control mice. Regional analysis of different midbrain areas containing dopaminergic neurons suggested that the increase in cell profile count occurs in a relatively homogeneous manner. Comparison of TH-immunoreactive cell size showed a tendency for smaller neurons in transgenic animals, but the difference was not statistically significant. We conclude that DBH:BDNF transgenic mice show increased number of TH-immunoreactive cells in the midbrain. We propose that BDNF rescues dopaminergic neurons from the perinatal period of developmental cell death as a consequence of increased anterograde transport of the neurotrophin via the coeruleonigral projection. CI - Copyright 1999 Wiley-Liss, Inc. FAU - Alonso-Vanegas, M A AU - Alonso-Vanegas MA AD - Department of Neurology and Neurosurgery, Cone Laboratory and Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada. FAU - Fawcett, J P AU - Fawcett JP FAU - Causing, C G AU - Causing CG FAU - Miller, F D AU - Miller FD FAU - Sadikot, A F AU - Sadikot AF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Comp Neurol JT - The Journal of comparative neurology JID - 0406041 RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 1.14.17.1 (Dopamine beta-Hydroxylase) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/analysis/*genetics/physiology MH - Dopamine/*metabolism MH - Dopamine beta-Hydroxylase/analysis/*genetics/metabolism MH - Heterozygote MH - Humans MH - Immunohistochemistry MH - Mesencephalon/cytology/*physiology MH - Mice MH - Mice, Transgenic MH - Neurons/*cytology/*physiology MH - Promoter Regions, Genetic EDAT- 1999/09/29 00:00 MHDA- 1999/09/29 00:01 CRDT- 1999/09/29 00:00 PHST- 1999/09/29 00:00 [pubmed] PHST- 1999/09/29 00:01 [medline] PHST- 1999/09/29 00:00 [entrez] AID - 10.1002/(SICI)1096-9861(19991025)413:3<449::AID-CNE7>3.0.CO;2-2 [pii] AID - 10.1002/(sici)1096-9861(19991025)413:3<449::aid-cne7>3.0.co;2-2 [doi] PST - ppublish SO - J Comp Neurol. 1999 Oct 25;413(3):449-62. doi: 10.1002/(sici)1096-9861(19991025)413:3<449::aid-cne7>3.0.co;2-2.