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

阿尔茨海默型老年性痴呆大脑神经回路退行性和再生性变化的研究：神经生长因子对成年大鼠大脑的影响

• 批准号: 02670524
• 负责人: IIZUKA Reiji
• 金额: $ 1.34万
• 依托单位: Juntendo University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670524/
• 关键词: Nerve growth factor (NGF); Brain transplantation; AChE-positive cells; Body weight gain; food intake; NGF concentration; male-female defference; AchE陽性ニュ-ロン; 体重変化; AchE組織化学

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

将胎鼠基底前脑组织移植到成年大鼠侧脑室，观察神经生长因子(NGF)对中枢胆碱能神经元的影响。植入插管的宿主动物脑室内注入NGF(20ug或100ug/ml)，持续两周。两周后，用AChE组织化学方法观察移植物胆碱能神经元和宿主脑腹侧苍白球(VP)胆碱能神经元的发育。输注NGF-20ug/ml组移植物AChE阳性细胞平均横截面积(x10±lt；-4；mm^2)明显大于对照组，而输注NGF-10µg/ml组AChE阳性细胞平均横截面积小于对照组。然而，宿主大脑VP中AChE阳性细胞的大小在任何一组中都没有显著差异。这些结果表明，对于…来说，存在一个最佳的神经生长因子浓度来增强胎儿基底的中枢胆碱能神经元。此外，脑室内注射NGF的大鼠与对照组相比，体重增加显著减少。脑室内注射NGF两周后，未移植的大鼠也得到了类似的结果。这些结果表明，NGF对成年大鼠的体重增加有抑制作用。输注NGF-20ug/ml的大鼠体重增加的变化与NGF-10oug/ml的大鼠没有显著差异，但NGF-20ug/ml组的每日摄食量与对照组没有显著差异。这些结果可能表明，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脑内注射被认为是治疗阿尔茨海默型老年性痴呆的一种潜在方法，在NGF注射治疗开始之前，有必要对本研究中观察到的反应的机制和功能意义进行更多的研究。最后，利用高灵敏的β-NGF双部位酶免疫分析系统，测定了Wistar品系幼年和老年雄性和雌性大鼠不同脑区的NGF水平。在研究的十个区域中，无论性别和年龄，每湿重组织的NGF含量在海马区都是最高的。3月龄雌性大鼠海马区NGF浓度与同龄雄性大鼠相当。此外，年轻男性和老年男性海马区的NGF水平没有显著差异。然而，老年雌性大鼠的NGF水平明显低于3月龄或4月龄雌性大鼠，因此老年Wistar大鼠的NGF水平存在显著的雌雄差异。较少

项目成果

Eto, K: "Intraventricular Infusion of Nerve Growth Factor (NGF) Suppresses Body Weight Gain of Adult Rats" Juntendo Medical Journal.

Eto, K：“神经生长因子 (NGF) 的脑室内输注可抑制成年大鼠的体重增加”Juntendo 医学杂志。

Eto, K: "Influence of Nerve Growth Factor on the Fetal Basal Forebrain Tissues Transplanted into the Brain of Adult Rats." Juntendo Medical Journal.

Eto, K：“神经生长因子对移植到成年大鼠大脑中的胎儿基底前脑组织的影响。”

Nishizuka,M.,Eto,K.,Arai,Y.,Iizuka,R.,et al: "Age-and Sex-Related Differences in the Nerve Growth Factor Distribution in the Rat Brain." Brain Research Bulletin. 27. 685-688 (1991)

Nishizuka,M.、Eto,K.、Arai,Y.、Iizuka,R.等人：“大鼠大脑中神经生长因子分布的年龄和性别相关差异。”

Nishizuka, M., Eto, K., Arai, Y., Iizuka, R., et al: "Age- and Sex-Related Differences in the Nerve Growth Factor Distribution in the Rat Brain." Brain Research Bulletin. 27. 685-688 (1991)

Nishizuka, M.、Eto, K.、Arai, Y.、Iizuka, R.等人：“大鼠大脑中神经生长因子分布的年龄和性别相关差异”。

江渡 江: "胎仔ラット前脳基底部のコリン系ニュ-ロンの脳室内移植におけるNGF投与の影響" 順天堂医学. 37(4).

Eto E：“NGF 给药对胎鼠基底前脑胆碱能神经元脑室内移植的影响”Juntendo Medical 37(4)。