Ganglioside-induced alterations in hippocampal cholinergic enzymes and Na,K-ATPase after fimbria-fornix transection.

Abstract

Previous biochemical findings suggest that exogenous gangliosides enhance cholinergic sprouting in the hippocampus after partial lesions of the septohippocampal pathway. To assess whether GM1 ganglioside accelerates the onset of this sprouting after complete lesions, we measured cholinergic enzymes and Na,K-ATPase activity in the hippocampus of rats with unilateral fimbria-fornix transection. At 14 and 18 days postlesion, histochemical staining showed that acetylcholinesterase (AChE) was almost completely eliminated in the hippocampus ipsilateral to the transection in untreated and GM1-treated rats. Biochemical assays confirmed that GM1 treatments did not increase AChE activity in the denervated hippocampus. Rather, there were significant reductions of AChE and choline acetyltransferase activities in the ipsilateral hippocampus relative to the contralateral value (P less than .001); and the reductions were greater in GM1-treated rats than in untreated controls (P less than .001). Na,K-ATPase activity in the ipsilateral hippocampus increased by 10.1% in GM1-treated rats, whereas it decreased by 21.7% in untreated controls (P less than .05). Since Na, K-ATPase is enriched in synaptic membranes, the increased activity of this enzyme may indicate that GM1 treatments stabilize surviving synaptic membranes and/or accelerate the onset of sprouting in the denervated hippocampus. The reductions in cholinergic enzymes, however, imply that the sprouting pathway must be noncholinergic.