Fate of septohippocampal neurons following intracerebroventricular injections of colchicine.

Injection of colchicine into the lateral ventricles (ICV) of rats results in a selective loss of neurons immunoreactive for choline acetyltransferase (ChAT) in the medial septum (MS) and a concomitant loss of acetylcholinesterase (AChE) positive fibers in the hippocampus. To determine if this loss of cholinergic cells is due to neuronal death, septohippocampal neurons were retrogradely labeled with fluoro-gold (FG) 1 week prior to the injection of colchicine. Numbers and sizes of FG-labeled and ChAT-immunoreactive neurons were assessed 3, 6, and 10 weeks after ICV colchicine. In line with previous observations, numbers of ChAT-immunoreactive cells were reduced to fewer than 50% of control in the MS and to fewer than 60% of control in the vertical limb of the diagonal band (vDB). Three weeks after ICV colchicine, numbers of FG-labeled neurons were reduced to 48% in the MS and 24% in the vDB. By 6 weeks, the number in the MS decreased further to 31% of control, whereas the number remained at 24% in the vDB. Ten weeks after colchicine, the numbers of retrogradely labeled cells in both the MS and vDB had decreased to 11% of control. The cells which remained were not reduced in cross-sectional area or in diameter. These data suggest that the selective loss of cholinergic neurons in the MS which occurs following ICV colchicine is due to neuronal death and not just loss of ChAT expression.