AGE-RELATED DEGENERATION OF THE SEROTONINERGIC FIBERS IN THE ZITTER RAT-BRAIN

The serotonin neuron system was studied using immunohistochemical and neurochemical techniques in titter mutant rats aged 1-14 months, which are characterized by abnormal metabolism of superoxides. The morpholo gy of the serotoninergic neuron system and the serotonin level in the zitter rat were compared to those of age-matched Sprague-Dawley (SD) r ats. Up to age 4 month, the density and distribution of serotoninergic fibers in the titter rat brain were similar to those of control rats. However, several serotoninergic fibers with abnormal morphology, char acterized by swollen varicosities, were observed in the cerebral corte x and caudate putamen of B-month-old titter rats. The density and dist ribution of these fibers in other regions of the brain were similar to those of control rats. The abnormal serotoninergic fibers increased i n number and extended into other regions of the brain such as the thal amus, hippocampus, and vestibular nucleus. On the other hand, the dens ity of normal serotoninergic fibers decreased throughout the brain of the 14-month-old titter rat. Abnormal serotoninergic fibers have also been reported in the brain of normal older (24 months) SD rats. Neuroc hemical analysis revealed lower levels of serotonin, and 5-hydroxyindo leacetic acid, in all cortical areas (prefrontal, parietal, and occipi tal cortices), the caudate putamen, and the hippocampus of 12-month-ol d titter rats. Levels differed significantly in the parietal cortex an d hippocampus between the titter and SD rats. Based on the morphologic al and neurochemical similarities, the present results suggest that ag e-related degeneration of serotoninergic fibers occurs in the titter r at brain. Furthermore, degeneration of serotoninergic fibers appears t o be induced by superoxide species. Thus, the titter rat may provide a good model for studying the neurotoxic effects of superoxide species on the serotoninergic neuron system. Synapse 38:62-70, 1998. (C) Wiley -Liss, Inc.