A study of degenerative and regenerative changes in neuronal circuitry in the brain of senile dementia of Alzheimer type : influence of nerve growth factor on adult rat brain

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Effects of nerve growth factor (NGF) on central cholinergic neurons were examined by transplantation of fetal rat basal forebrain tissues into the lateral ventricle of adult rats. The host animals implanted with a cannula were infused with NGF (20ug or 100ug/ml) intraventricularly for two weeks. Two weeks later, we observed the development of the cholinergic neurons in the grafts and the cholinergic neurons in the ventral globus pallidus (VP) of the host brain used by AChE-histochemistry. The average cross-sectional size (x10^<-4>mm^2) of AChE-positive cells in the grafts in the animals infused with NGF-20ug/ml was significantly- larger than that in the controls, but that in the animals infused with NGF-10 Oug/ml was smaller the size. However, the size of the AChE-positive cells in the VP of host brains did not differ significantly in any of the groups. These findings suggest that there is an optimal NGF concentration for enhancing the central cholinergic neurons in the fetal basal for … More ebrain graft tissues.In addition, the rats infused intraventricularly with NGF showed a significant reduction in body weight gain compared to the controls. The similar results were obtained in the rats without grafts following intraventricular infusion of NGF for two weeks. These findings indicated that NGF exerted an inhibitory influence on body weight gain in adult rats. 'The changes of body weight gain in the rats infused with NGF-20ug/ml did not differ significantly from those with NGF-10 Oug/ml. however, the amounts of daily food intake in NGF-trated group did not differ significantly from those in controls. Thes result may suggest that there is no correlation between the change in daily food intake and the reduction in body weight gain. Since administration of exogenous NGF into the brain is being considered as a potential therapy for senile dementia of Alzheimer type, more research is necessary the mechanisms and functional significance of the response observed in this study before NGF infusion therapy is initiated.Finally, Levels of the NGF have been measured in various brain regions of young and aged male and female rats of Wistar strain by means of a highly sensitive two-site enzyme immunoassay system for beta-NGF. Among the ten regions examined, the amount of NGF per wet weight of tissue was found to be highest in the hippocampus, irrespective of the sex and age. The NGF concentration in the hippocampus of female rats at 3 months of age was comparable to that of same age males. Further, there was no significant difference in the NGF levels of the hippocampus between young and aged males. However, the NGF level was significantly lower in aged females as compared to that in 3- or 4-month-old females, and hence the marked male-female defference was found in the NGF levels in aged Wistar rats. Less