Association of learning and memory impairments with changes in the septohippocampal cholinergic system in rats with kaolin-induced hydrocephalus

OBJECTIVE: The septohippocampal cholinergic (SHC) system plays an important role in the maintenance of normal memory and learning. However, the fact that memory and learning impairments under hydrocephalic conditions are directly related to the SHC system is less well known. We investigated the relationships between pathological changes in SHC neurons and impairments in memory and learning among hydrocephalic rats. METHODS: Rats with kaolin-induced hydrocephalus were prepared with injections of kaolin suspension into the cisterna magna. Learning and memory performance was assessed with the passive avoidance and Morris water maze tests. Ventricular sizes were measured for the lateral and third ventricles. Acetylcholinesterase and choline acetyltransferase immunostaining was performed to investigate degenerative changes in cholinergic neurons in the medial septum and hippocampus. RESULTS: Hydrocephalic rats demonstrated significant learning and memory impairments in the passive avoidance and Morris water maze tests. Decreased hesitation times in the passive avoidance test and markedly increased acquisition times and decreased retention times in the Morris water maze test indicated learning and memory dysfunction among the hydrocephalic rats. The numbers of cholinergic neurons in the medial septum and hippocampus were decreased in the hydrocephalic rats. The decreases in choline acetyltransferase and acetylcholinesterase immunoreactivity were significantly correlated with enlargement of the ventricles. CONCLUSION: Impairment of spatial memory and learning may be attributable to degeneration of SHC neurons. These results suggest that learning and memory impairments in rats with kaolin-induced hydrocephalus are associated with the dysfunction of the SHC system induced by ventricular dilation.