NERVE GROWTH FACTOR PREVENTS BASAL FOREBRAIN NGF-R POSITIVE NEURONAL LOSS AFTER FIMBRIA FORNIX TRANSECTION
Long Dahong; Yao Zhibin; He Yunshao(Department of Brain Research, Sun Yat-Sen University of Medical Sciences, Guangzhou)
The cholinergic neurons of the hasal forebrain are believed to be involved in the functional processes of learning and memory.Impaired memory is a cardinal symptom in the diagnosis of Alzheimer's disease and presenile dementia of the Alzheimer's type. A morpbological correlation of the disease is the shrinkage and/or death of cholinergic neurons in the hasal forebrain and a loss of choline acetyltransferase in the cortex and hippocampus. Nerve growth factor has been shown to be a neurotrophic factor for the hasal forebrain cholinergic neurons. Several investigators have reported the prevention by chronic intraventricular NGF treatment from the massive disappearance of cholinergic neurons in the medial septum and the vertical limbs of the diagonal band of Broca in adult rat. But it is so far not known wether cholinergic neurons in aged animal are also responsive to NGF, which is very important in investigating the use of NGF in the treatment of Alzheimer's disease. The aim of the present work is to investigate effect of NGF on the lesioned hasal forebrain cholinergic system of aged animal model.Aged male SD rats were subjected to left fimbria fornix transection and received continuous infusion Cyt. c'or NGF into the cerebroventricular space. Treatment were initiated immediately after lesion and ended after one month. On the thirtieth pact-lesion day brains were processed for NGF-R immunocytochemistry. In the present study we used quantitative morphornetric tech niques to evaluate the response of these axotomized neurons to a constant infusion of nerve growth factor. Neurons in the rat MS and VDB underwent a rapid and severe cell loss after transection of the unilateral fimbria fornix. By 30 days, the extent of neuronal loss was 59.4% of NGF-R-labeled cells in the MS and 37.74% of NGF-R-labeled cells in the VDB on the lesioned side.The area, the largest and the smallest diameters of the cell in MS/VDB were all significantly decreased (P0.01 ). But 1 30 days following a continuous infusion of NGF in the lateral ventricle, the infusion not only preserves the total number of NGF-R- positive cells but also maintains at normal levels in the size and shape of the saved neurons.The finding indicated that hasal forebrain cholinergic neurons in aged animal was responsive to NGF similarly to the a'lult animal. These findings further supported the consideration that NGF may be a potential therapeutic agent for the treatment of Alzheimer's disease.