TNF-ALPHA EXPRESSED IN THE BRAIN OF TRANSGENIC MICE LOWERS CENTRAL TYROXINE HYDROXYLASE IMMUNOREACTIVITY AND ALTERS GROOMING BEHAVIOR

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine involved in a wi de range of biological effects both in physiological and non-physiolog ical conditions. It is also produced in the central nervous system (CN S) where it has been implicated in reparative processes after traumati c injuries and in CNS demyelination, neurodegeneration and inflammatio n. Using transgenic mice (Tg-m) expressing TNF-alpha specifically in t he CNS, we showed that the overexpression of this cytokine reduced tyr oxine hydroxilase immunoreactivity (TH-ir) in the caudate-putamen and in the dorsomedial hypothalamic areas and impaired grooming behavior. We also showed that this behavior is increased following anti-nerve gr owth factor injection. These findings support the hypothesis, proposed by others, that TNF-alpha is involved in the degenerative processes w hich occur in Parkinson's disease. (C) 1997 Elsevier Science Ireland L td.