Institute of Anatomy and Cell Biology, Medical College, Zhejiang University, China.
Int J Neurosci. 2010 Sep;120(9):602-8. doi: 10.3109/00207454.2010.503911.
The senescence-accelerated mouse (SAM) is an autogenic senile murine model characterized by early cognitive impairment and age-related deterioration of learning and memory. The present study investigated the alternations of neuronal nitric oxide synthase (nNOS) expression in frontal cortex and hippocampus in the aging process of SAM-prone 8 (SAMP8) and SAM-resistant 1 (SAMR1) mice. The results demonstrated that the expression of nNOS was upregulated in the frontal cortex, but downregulated in the hippocampus in SAMP8. Further, age-related increases of astrogliosis were seen in the cortex and hippocampi of aged SAMP8 and SAMR1, as revealed by the expression of the astrocyte specific marker, glial fibrillary acidic protein (GFAP). Indeed, astrogliosis in aged SAMP8 was significantly greater than that of aged SAMR1. Our results suggest the possibility of a correlation between the downregulation of nitric oxide (NO) in the hippocampus and reported learning and memory deficits in SAMP8. However, the toxic effects of NO and age-related increases of astrogliosis, may have contributed to abnormal alterations in metabolism and neurochemical mechanisms in aged SAMP8.
衰老加速小鼠（SAM）是一种自发性衰老的啮齿动物模型，其特征是早期认知障碍和与年龄相关的学习和记忆能力下降。本研究探讨了易衰老型 SAM 品系 8（SAMP8）和抗衰老型 SAM 品系 1（SAMR1）小鼠衰老过程中额叶皮层和海马神经元型一氧化氮合酶（nNOS）表达的变化。结果表明，nNOS 在 SAMP8 的额叶皮层中表达上调，但在海马中表达下调。此外，衰老 SAMP8 和 SAMR1 的皮质和海马中星形胶质细胞标志物胶质纤维酸性蛋白（GFAP）的表达表明星形胶质细胞增生。事实上，衰老 SAMP8 中的星形胶质细胞增生明显大于衰老 SAMR1。我们的结果表明，海马中一氧化氮（NO）的下调与 SAMP8 中报道的学习和记忆缺陷之间可能存在相关性。然而，NO 的毒性作用和与年龄相关的星形胶质细胞增生可能导致衰老 SAMP8 中代谢和神经化学机制的异常改变。
