Tryptophan hydroxylase in hippocampus and midbrain following unilateral injection of 5,7-dihydroxytryptamine

We have previously shown using anatomical methods that partial denervation of the rat hippocampus by removal of serotonergic (5-HT) fibers in the cingulum bundle induces sprouting of intact 5-HT fibers reaching the hippocampus in the fornix-fimbria. The biochemical properties of collateral sprouting fibers have remained largely uncharacterized. Thus, the rate-limiting enzyme in 5-HT synthesis, tryptophan hydroxylase (TPOH), was studied to determine whether new sprouts possess the ability to synthesize 5-HT. Unilateral stereotaxic injections of 5 micrograms 5,7-dihydroxytryptamine were made into the cingulum bundle of adult rats in order to produce partial and selective deafferentation of the hippocampus. Following injection, enzyme activity in the hippocampus declined gradually and bilaterally, reaching minimal levels by 7 days post-lesion. This decrease in enzyme activity was paralleled by a decrease in the Vmax and an increase in the Km of TPOH for tryptophan. Enzyme activity began to increase after 14 days post-lesion, reaching maximal levels by 60 days, but never returning to pre-lesion levels in the ipsilateral side. In midbrain, site of neuronal cell bodies of hippocampal 5-HT projections, enzyme activity gradually increased, reaching a maximum by 28 days after the lesion. These results indicate that 5-HT fibers remaining in the hippocampus following partial denervation are able to compensate biochemically for those removed by cingulum bundle lesions. Biochemical compensation may depend on increased synthesis of TPOH molecules in midbrain cell bodies with subsequent transport into sprouts of intact fibers in the hippocampus.