Dass Biplob, Kladis Theodora, Chu Yaping, Kordower Jeffrey H
Department of Neurological Sciences, Rush University Medical Center, 1735 W. Harrison Street, Chicago, IL 60657, USA.
Neurobiol Aging. 2006 Jun;27(6):857-61. doi: 10.1016/j.neurobiolaging.2005.04.002. Epub 2005 Jun 13.
Parkinson's disease is characterized by bradykinesia, rigidity and a resting tremor and the underlying basis for those symptoms is the loss of dopaminergic cells in the nigrostriatal system. Similar to PD, an age-related decrease locomotor activity and the expression of tyrosine hydroxylase immunoreactivity has been observed in rhesus monkeys, but the reason for this decrease in dopaminergic function remains to be elucidated. Trophic factors such as glial cell line derived neurotrophic factor (GDNF) and neurturin sustain the dopaminergic phenotype in midbrain neurons and act through a common receptor tyrosine kinase (RET). Examination of RET expression by immunohistochemistry was performed on sections of tissue containing the substantia nigra pars compacta of young, middle, and old aged rhesus monkeys. Stereological estimates of the number and cellular area of RET-immunoreactive cells found no change with age. Estimation of changes in RET protein using fluorescence intensity measurement was also similar across age groups. The results indicate that the mechanisms of GDNF and neurturin signaling remain intact with age, and therefore these trophic factors may be able to enhance the dopaminergic function of neurons in the nigrostriatal system, when administered to individuals of any age.
帕金森病的特征是运动迟缓、僵硬和静止性震颤,这些症状的潜在基础是黑质纹状体系统中多巴胺能细胞的丧失。与帕金森病相似,在恒河猴中也观察到与年龄相关的运动活动减少以及酪氨酸羟化酶免疫反应性的表达,但多巴胺能功能下降的原因仍有待阐明。胶质细胞源性神经营养因子(GDNF)和神经营养素等营养因子维持中脑神经元中的多巴胺能表型,并通过共同的受体酪氨酸激酶(RET)发挥作用。通过免疫组织化学对含有年轻、中年和老年恒河猴黑质致密部的组织切片进行RET表达检测。对RET免疫反应性细胞的数量和细胞面积进行体视学估计,未发现随年龄变化。使用荧光强度测量对RET蛋白变化的估计在各年龄组中也相似。结果表明,GDNF和神经营养素信号传导机制随年龄保持完整,因此,当给予任何年龄的个体时,这些营养因子可能能够增强黑质纹状体系统中神经元的多巴胺能功能。