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NEUROBIOLOGICAL EFFECTS OF COLCHICINE: MODULATION BY NERVE GROWTH FACTOR
Citation:
Barone, Jr., S., P. Tandon, M. Bonner, AND H. Tilson. NEUROBIOLOGICAL EFFECTS OF COLCHICINE: MODULATION BY NERVE GROWTH FACTOR. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-92/107 (NTIS PB92158633), 1992.
Description:
To study the effects of exogenously applied nerve growth factor (NGF) on colchicine-induced neurodegeneration in the dentate gyrus of the rat hippocampal formation, male Fischer 344 rats (n=75) weighing 275-325 grams received colchicine [COLCH; 2.5 ug/site in 0.5 ul of artificial cerebrospinal fluid (ACSF)] or ACSF alone into the dorsal hippocampus. mmediately following COLCH reatment a chronic indwelling cannula was implanted unilaterally in the lateral ventricle and a modified Alzet mini-osmotic pump (0.25 ul/Mr) containing either purified Beta NGF 110 ng/l in ACSF] or cytochrome C [20 ng/ul in ACSF] was attached to a connector cannula and cemented in place. ne week later, animals were tested in activity chambers for a minute session. GF treatment reduced COLCH-induced hyperactivity. nimals were sacrificed at 3 or 12 weeks post-lesion. t each time point animals were assigned for either neurochemical or morphological analysis. arbachol-stimulated phosphatidyl inositol (PI) turnover was performed after incorporation of [3H]-inositol into hippocampal slices. t 3 weeks, carbachol (CARB)-induced PI turnover was not significantly altered for any treatment. owever, 12 weeks after the lesion, CARB stimulation of PI was increased only in the COLCH/ACSF group. rior treatment with NGF significantly reduced the compensatory hyperstimulation in colchicine-treated rats. or morphological analysis sections were Nissl-stained, reacted histochemicallY for acetylcholinesterase (AChE) or stained immunocytochemically for choline acetyltransferase (ChAT). T 3 or 12 weeks post-lesion COLCH treatment increased AChE staining in the CA3 region of the hippocampus, whereas NGF treatment did not alter AChE staining in the hippocampus at 3 or 12 weeks. here was no difference in the number of septal ChAT immunoreactive cell bodies in the brains of controls or colchicine-treated rats at either 3 or 12 weeks post-lesion. owever, at 3 weeks post-lesion the number of ChAT immunoreactive cell bodies was significantly greater for both NGF-treated groups. t l2 weeks post-lesion, there was no significant difference in the number of ChAT-IR cell bodies in the media] septum for any of the treatment groups. esults from this study indicate that intraventricular NGF can modify colchicine-induced compensatory changes in hippocampal signal transduction and has transitory influences on cholinergic cells in the medial septum.