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.