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.


CONCLUSIONS
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.
Shim
Insop
I
Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Seoul, Korea.
Ha
Yoon
Y
Chung
Jin Young
JY
Lee
Hye-Jung
HJ
Yang
Kook Hi
KH
Chang
Jin Woo
JW
D000818:Animals; D000930:Antidiarrheals / Q000009:adverse effects*; D001362:Avoidance Learning / Q000502:physiology; D002799:Cholinergic Fibers / Q000473:pathology* / Q000502:physiology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006849:Hydrocephalus / Q000139:chemically induced* / Q000150:complications* / Q000473:pathology; D007616:Kaolin / Q000009:adverse effects*; D007859:Learning Disabilities / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020665:Septum of Brain / Q000473:pathology* / Q000503:physiopathology
D000930:Antidiarrheals; D007616:Kaolin