权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular Biological Research related to Developmental Mechanism and New Medical Treatment of Congenital Hydrocephalus

先天性脑积水发育机制及新药治疗相关的分子生物学研究

基本信息

批准号：
05454403
负责人：
SATO Kiyoshi
金额：
$ 1.47万
依托单位：
Juntendo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454403/
关键词：
Congenital Hydrocephalus Forebrain Cholinergic System Nerve Growth Factor Cytokin C-Type Natriuretic Peptide Intracranial Pressure CSF Outflow Resistance Hydrocephalic HTX-rat 先天性水頭症ラット C-type natriuretic peptide receptor GC-B RT-PCR

项目摘要

(1) We have demonstrated in the congenital hydrocehalic HTX-rats that the progression of hydrocephalus impaired the forebrain cholinergic system, whose integrity is essential for learning and memory functions. This result using neurochemical methods has supported our previous findings, that delayd treatment of congenital hydrocephalus was related to the impairment of learning ability in the congenital hydrocephalic HTX rats.Furthermore it was interesting that nerve growth factor (NGF) and some cytokins which play important roles in survival and differentiation of the neuron were increased in the cortex of congenital hydrocephalic HTX rats.The NGF and some cytokins increase in the cortex was supposed to depend on the secretion of reactive astrocytes prominently appearing in the affected cortex and on the accumulation due to impaired retrograde axonal transport of NGF.(2) Intraventricular injection of C-type natriuretic peptide (CNP) in hydroceohalic HTX rats was found to be effective in lowering intracranial pressure and CSF outflow resistance. The results of the present investigation would appear to suggest that CNP could be another candidate for medical treatment of congenital hydrocephalus. The problem regarding the intrinsic regulation of CNP,and the mechanism for lowering intracranial pressure and CSF outflow resistance, remain for further study and investigation.(3) The point mutation of adhesion molecule L1 gene has been demonstrated in human X-linked hydrocephalus, but we could not identify this point mutation in hydrocephalic HTX-rats. Our investigations have shown that there was less gene expression of functional C-type natriuretic peptide receptor in the brain of hydrocephalic HTX-rats than in Wister rats. This result would suggest that the transcription factor, which regulates the C-type natriuretic peptide receptor gene, may be genetically abnormal, but we need further study and investigation.

(1)我们已经证明，在先天性脑积水HTX-大鼠，脑积水的进展损害前脑胆碱能系统，其完整性是必不可少的学习和记忆功能。使用神经化学方法的这一结果支持了我们以前的发现，先天性脑积水的延迟治疗与先天性脑积水HTX大鼠学习能力的损害有关，而且神经生长因子（NGF）在先天性脑积水HTX大鼠学习能力的改变中起重要作用。脑积水HTX大鼠脑皮质内神经元存活和分化中起重要作用的细胞因子含量增加，皮质中的增加被认为取决于显著出现在受影响皮质中的反应性星形胶质细胞的分泌和由于受损的NGF的逆行轴突运输而导致的积累。(2)脑室内注射C型利钠肽（CNP）可有效降低脑积水HTX大鼠的颅内压和脑脊液流出阻力。本研究的结果似乎表明CNP可能是先天性脑积水药物治疗的另一种候选药物。关于CNP的内在调节以及降低颅内压和CSF流出阻力的机制的问题仍有待进一步研究和调查。(3)在人类X连锁脑积水中发现了黏附分子L1基因的点突变，但在脑积水HTX大鼠中未发现该点突变。我们的研究表明，脑积水HTX大鼠脑中功能性C型利钠肽受体的基因表达低于Wister大鼠。这一结果提示调控C型利钠肽受体基因的转录因子可能存在遗传异常，但还需进一步研究。