NEURO-GLIAL NEUROTROPHIC INTERACTION IN THE S-100-BETA RETARDED MUTANT MOUSE (POLYDACTYLY-NAGOYA) .1. IMMUNOCYTOCHEMICAL AND NEUROCHEMICAL STUDIES

The homozygote of a mouse strain with genetic polydactyly (Polydactyly Nagoya; Pdn) shows several brain abnormalities, and significant decre ase of S-100 beta in the brain(43). In order to clarify the effects of the retarded production of S-100 beta on the development of monoamine rgic neuronal systems and supporting glial cells, immunocytochemical s tudies of tyrosine hydroxylase (TH), serotonin (5-HT), S-100 beta and glial fibrillary acidic protein (GFAP). In addition, high-performance liquid-chromatography (HPLC) measurements of serotonin and 5-hydroxyin doleacetic acid (5-HIAA) of homozygote (Pdn/Pdn) mouse were examined, and the results were compared with those of other genotypes; heterozyg ote (Pdn/+) and wild type (+/+) mice. In all types of mice, S-100 beta positive cells and serotonergic fibers were widely distributed throug hout the brains and serotonergic cell bodies were located in the brain stem. However, the hippocampus and caudo-dorsal cortex of Pdn/Pdn mous e were markedly reduced in S-100 beta positive cells and in serotonerg ic fibers. Furthermore, abnormal distribution of GFAP positive cells a nd fibers were observed in the neocortex and hippocampus of Pdn/Pdn br ain. No differences were seen in the distribution of TH neurons or fib ers distribution. In the HPLC study, the content of 5-HT and 5-HIAA of the hippocampus and cortex of Pdn/Pdn mouse was lower than those of P dn/+ and +/+ mice. The present results suggest that the developmental defect of serotonergic fibers in the Pdn mutant mouse is correlate to the deficiency of S-100 beta in the astrocyte of this mutant.