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

采用胎鼠基底前脑移植成年大鼠侧脑室，观察神经生长因子（NGF）对中枢胆碱能神经元的影响。植入导管的宿主动物分别在脑室内注射NGF （20ug或100ug/ml）两周。2周后，我们用乙酰氨基酚（ache）组织化学方法观察移植物和宿主大脑苍白球腹侧（VP）胆碱能神经元的发育情况。NGF-20ug/ml灌注组ache阳性细胞的平均横截面尺寸（x10^<-4>mm^2）明显大于对照组，而ngf - 10ug /ml灌注组ache阳性细胞的平均横截面尺寸小于对照组。然而，宿主脑VP中ache阳性细胞的大小在任何组中都没有显着差异。这些研究结果表明，存在一个最佳的NGF浓度来增强胎儿基底中枢胆碱能神经元。此外，与对照组相比，脑室内注入NGF的大鼠体重增加明显减少。在没有移植物的大鼠脑室内灌注NGF两周后，也获得了类似的结果。这些发现表明，NGF对成年大鼠的体重增加具有抑制作用。注射NGF-20ug/ml的大鼠体重增加的变化与注射ngf - 10ug /ml的大鼠没有显著差异。然而，神经生长因子处理组的每日食物摄入量与对照组没有显著差异。这一结果可能表明，每日食物摄入量的变化与体重增加的减少之间没有相关性。由于外源性NGF输注脑被认为是治疗老年痴呆症的一种潜在方法，因此在启动NGF输注治疗之前，需要对本研究中观察到的反应机制和功能意义进行更多的研究。最后，利用高度敏感的-NGF双位点酶免疫测定系统，测定了Wistar菌株年轻和老年雄性和雌性大鼠大脑各区域的NGF水平。在检查的十个区域中，无论性别和年龄，每湿重组织的NGF量在海马中最高。3月龄雌性大鼠海马NGF浓度与同龄雄性大鼠相当。此外，年轻雄性和老年雄性海马的NGF水平没有显著差异。然而，老龄母鼠的NGF水平明显低于3、4月龄母鼠，因此老龄Wistar大鼠的NGF水平存在明显的雌雄差异。少

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