Characterization of dopaminergic midbrain neurons in a DBH : BDNF transgenic mouse

The neurotrophin brain-derived neurotrophic factor (BDNF) has been implicat ed in the survival and differentiation of central nervous system neurons, i ncluding dopaminergic cells in culture. To determine whether BDNF might pla y a role in the development of dopaminergic neurons in vivo, we used a prev iously characterized transgenic mouse (DBH:BDNF) that overexpresses BDNF in adrenergic and noradrenergic neurons as a result of fusion of the BDNF gen e to the dopamine beta-hydroxylase (DBH) gene promoter. We quantified dopam inergic 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 t hat the mean number of dopaminergic neurons in the four selected midbrain s ections was 52% greater tone-way analysis of variance, (P < 0.0005) in tran sgenic 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:B DNF transgenic animals was confirmed by analysis of the pars compacta of th e substantia nigra on Nissl-stained sections. Surface area of the reference region of interest containing TH-immunoreactive neurons was similar in tra nsgenic and control mice. Regional analysis of different midbrain areas con taining dopaminergic neurons suggested that the increase in cell profile co unt occurs in a relatively homogeneous manner. Comparison of TH-immunoreact ive 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 th e midbrain. We propose that BDNF rescues dopaminergic neurons from the peri natal period of developmental cell death as a consequence of increased ante rograde transport of the neurotrophin via the coeruleonigral projection. (C ) 1999 Wiley-Liss, Inc.