NEURAL AND ASTROGLIAL EFFECTS OF A CHRONIC PARACHLOROPHENYLALANINE-INDUCED SEROTONIN SYNTHESIS INHIBITION

Serotonin (5HT) is one of the classical neurotransmitters expressed ea rlier in the embryonic rat brain, and it was proposed as a development al signal in the central nervous system. In the adult brain, 5HT seems to be involved in neuronal plasticity. It was postulated that S-100 p rotein, a glial neurotrophic factor, could be modulated by 5HT probabl y through the glial 5HT(1A) receptors. Ln a model of chronic inhibitio n of endogenous 5HT synthesis produced by the daily administration of parachlorophenylalanine (PCPA) for 2 wk, we have studied by immunohist ochemical methods and digital morphometric analysis the expression of two proteins present in rat brain astrocytes: glial fibrillary acidic protein (GFAP) and S-100 protein. The effectiveness of the PCPA treatm ent was tested by the use of specific anti-5HT antibodies that showed absence of 5HT fibers in 5HT innervation areas like frontal cortex and hippocampus. Different effects of PCPA treatment on serotoninergic ra phe nuclei were observed: dorsal raphe nucleus (DRN) seemed to be more sensitive to the PCPA's action than ventral raphe nucleus (VRN). In D RN and in the two 5HT innervation areas studied, glial cells responded to the 5HT depletion induced by PCPA showing astrocytes with large an d tortuous processes. Astrocytes from 5HT-depleted regions showed high er immunostaining for S-100 protein than controls. There was not any m odification in optical density of S-100 protein immunostaining in VRN, the area less sensitive to PCPA treatment. These observations indicat ed that astrocytes are sensitive to the 5HT level, and in presence of low 5HT concentration in the intercellular space, astrocytes could rea ct by synthesizing glial proteins like GFAP and S-100 protein.