Inducible expression of tryptophan hydroxylase without serotonin synthesisin hypothalamic dopaminergic neurons

In the present study we have further studied the previous findings that rat hypothalamic dopaminergic neuronal cell groups may express tryptophan hydr oxylase (TpH), the serotonin synthesizing enzyme, without a detectable sero tonin synthesis. Chemical and mechanical neuronal injuries, namely colchici ne treatment and axonal transection, respectively, were performed, and dist ributions of neurons exhibiting immunoreactivity for TpH and/or tyrosine hy droxylase (TH), the dopamine synthesizing enzyme, were analyzed throughout the hypothalamic periventricular and arcuate nuclei. After colchicine treat ment there was a statistically significant 87% (P = 0,01) increase in the n umber of TpH expressing neurons, while TH expression remained essentially s imilar. Axonal transection resulted also in a statistically significant 131 % (P < 0,01) increase in the number of TpH expressing neurons, while TH exp ression was not significantly altered. All TpH expression coexisted with TH expression, and the induction of TpH expression by neuronal injuries occur red evenly throughout the rostrocaudal length of the territory studied. A p ossible serotonin synthesis by TpH was examined by giving drugs that increa se brain serotonin synthesis, but no immunohistochemically detectable serot onin synthesis could be found in any of the TpH expressing neurons. Finally the possibility was studied that the relative shortage of the cofactor tet rahydrobiopterin would limit serotonin synthesis. However, an administratio n of tetrahydrobiopterin did not result in detectable serotonin synthesis i n these neurons. Taken together these results suggest that dopaminergic neu rons in the hypothalamic periventricular and arcuate nuclei are able to exp ress TpH, this expression is induced after neuronal injury, and this induct ion occurs similarly throughout the territories studied. TpH expression occ urs independently of TH expression, and the newly expressed TpH appears not to synthesize serotonin, regardless of pharmacological pretreatments. Thus , our findings (i) support the idea that neurons may possess inducible expr ession of nonfunctional transmitter-synthesizing enzymes, in this case TpH, and (ii) suggest that expression of an enzyme synthesizing a certain trans mitter may not necessarily imply the corresponding transmitter phenotype. ( C) 1999 Academic Press.