Xie Fang, Fu Han, Zhang Jiu-Cong, Chen Xue-Feng, Wang Xiao-Liang, Chen Jun
Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, Gansu 730050, P.R. China.
Mol Med Rep. 2014 Jul;10(1):217-22. doi: 10.3892/mmr.2014.2227. Epub 2014 May 9.
Aging of the nervous system leads to impairments in cognition and motor skills, and is a major risk factor for several neurological disorders. Recently, numerous nerve function deficits that appear with aging have been found to be a consequence of myelin abnormalities; however, the genetic mechanism of the age‑related alterations in the myelin sheath has not yet been fully elucidated. In the present study, the morphology of the myelin sheath in the optic nerve of rats was analyzed at 10 time‑points throughout life. Marked alterations in the myelin sheath were observed in aging and aged optic nerves, and these became progressively more severe with time. To determine the biological processes affected by aging in the myelin sheath, the age‑related profiling of the myelin sheath in rat optic nerves was established using microarray hybridization at 10 time‑points throughout life, between birth and senescence. From the results, 3,826 transcripts associated with the age‑related alterations in the myelin sheath of the optic nerve were identified. It was found that the biological processes most significantly altered by aging were lipid metabolism, the immune response and transmitter transport. This suggests that the downregulation of lipid synthesis genes and the upregulation of immune and neurotransmitter transport genes in aging may be the genetic basis for the age‑related alterations observed in the myelin sheath.
神经系统的老化会导致认知和运动技能受损,并且是多种神经疾病的主要风险因素。最近,已发现随着衰老出现的许多神经功能缺陷是髓鞘异常的结果;然而,髓鞘中与年龄相关的改变的遗传机制尚未完全阐明。在本研究中,在大鼠整个生命过程中的10个时间点分析了视神经中髓鞘的形态。在衰老和老年视神经中观察到髓鞘有明显改变,并且这些改变随着时间的推移逐渐变得更加严重。为了确定衰老影响髓鞘的生物学过程,在出生至衰老的整个生命过程中的10个时间点,使用微阵列杂交建立了大鼠视神经中髓鞘的年龄相关图谱。从结果中,鉴定出3826个与视神经髓鞘中与年龄相关的改变相关的转录本。发现受衰老影响最显著的生物学过程是脂质代谢、免疫反应和递质转运。这表明衰老过程中脂质合成基因的下调以及免疫和神经递质转运基因的上调可能是在髓鞘中观察到的与年龄相关改变的遗传基础。