Serotonin hyperinnervation in the adult rat ventral mesencephalon following unilateral transection of the medial forebrain bundle. Correlation with reactive microglial and astroglial populations

We have previously studied changes in the serotoninergic and dopaminergic n igrostriatal systems following transection of the medial forebrain bundle a nd found a long-term axotomy-induced increase in the levels of serotonin an d its main metabolite, 5-hydroxyindolacetic acid in substantia nigra [Vener o et al. (1997) J. Neurochem. 68, 2458-2468]. In an attempt to find a ratio nale for this effect, we have performed an immunohistochemical study. Trans ection of the medial forebrain bundle of the rat interrupted most of the as cending serotoninergic pathways from the raphe nuclei as revealed by seroto nin immunoreactivity. While serotonin immunostaining was almost absent in s triatum, it doubled in the ventral mesencephalon at 21 days postlesion, Thi s axotomy-induced increase was accompanied by an increased density of the s erotonin nerve terminal network in the ipsilateral substantia nigra and ven tral tegmental area. The increase in serotonin immunoreactivity was in line with the measured levels of serotonin and 5-hydroxyindolacetic acid in sub stantia nigra. In addition, the distribution pattern of glial fibrillary ac idic protein-immunoreactive astrocytes and OX42-immunoreactive microglia co rrelated highly with the location of increased serotonin fibre density in t he ventral mesencephalon, especially in ventral tegmental area and in the m ost medial part of substantia nigra. We suggest that a pruning effect may u nderly the axotomy-induced increase in serotonin immunoreactivity in the ve ntral mesencephalon, and further, that activated astroglia and microglia ma y play a role in directing serotoninergic axonal regeneration following axo tomy. (C) 1999 IBRO. Published by Elsevier Science Ltd.