COLCHICINE INDUCES THE GAP-43 GENE-EXPRESSION IN RAT HYPOTHALAMUS

Injection of colchicine, a mitogen inhibitor, in the dorsal third vent ricle induced the expression of the growth associated protein-43 (GAP- 43) mRNA in some groups of cells of the adult rat brain. These mRNAs w ere detected by in situ hybridization histochemistry using an alkaline phosphatase labeled oligonucleotide probe. A substantial up-regulatio n of GAP-43 mRNA was noticed by the increase of both the number of pos itive cells and the intensity of the hybridization signal. These chang es were observed in the hypothalamic nuclei located near the ventral t hird ventricle, namely the preoptic area, the supraoptic nucleus, the peri- and the paraventricular nuclei of the hypothalamus, the dorsal s ubnucleus of the ventromedial nucleus, the arcuate nucleus and the pos terior part of the peri-mammillary region. Such abundant GAP-43 mRNA p ositive cells have not been observed in control adult rat hypothalamus . Since the positive cell number and shape initially suggested that th ese were neurons or astrocytes, double labeling in situ hybridization using both radioactive (for the detection of GFAP mRNA as a marker of astrocyte) and non-radioactive (for the detection of GAP-43 mRNA) prob es was carried out. This demonstrated that these GAP-43 mRNA positive cells were not astrocytes. In addition enhanced GAP-43 mRNA expression was also found in some neuronal component, particularly in neurosecre tory magnocells of the pareaventricular and the supraoptic nuclei. Thi s up-regulation was further confirmed by the Northern blot analysis. A bout five fold increase in GAP-43 mRNA in the colchicine-treated hypot halamic tissue was shown. These results suggest that GAP-43 mRNA was u p-regulated by colchicine in some neurons of the central nervous syste m as well as in those of peripheral nervous system, although the preci se mechanism of the up-regulation is not clear.