Effects of acetyl-L-carnitine treatment and stress exposure on the nerve growth factor receptor (p75NGFR) mRNA level in the central nervous system of aged rats.
作者信息
Foreman P J, Perez-Polo J R, Angelucci L, Ramacci M T, Taglialatela G
机构信息
Institute for Research on Senescence Sigma Tau, Pomezia, Italy.
There is growing evidence that the nerve growth factor protein (NGF), a neurotrophic factor for peripheral and central nervous system (CNS) neurons, may play a role in the modulation of the hypothalamo-pituitary-adrenocortical axis (HPAA). While NGF binding is decreased in rodent CNS after stress exposure, this reduction is prevented by treatment with Acetyl-L-Carnitine (ALCAR), a chemical substance able to prevent some degenerative events associated with aging. 2. The authors studied the effect of cold stress on the low-affinity NGF receptor (p75NGFR) mRNA levels in the basal forebrain and cerebellum of aged rats chronically treated with ALCAR. 3. The present results show that ALCAR abolished the age-associated reduction of p75NGFR mRNA levels in the basal forebrain of old animals, but did not affect the response to stress stimuli. 4. Also, treatment with ALCAR maintained p75NGFR mRNA levels in the cerebellum of old animals at levels almost identical to those observed in young control animals. 5. These results suggest a neuroprotective effect for ALCAR on central cholinergic neurons exerted at the level of transcription of p75NGFR. The restoration of p75NGFR levels could increase trophic support by NGF of these CNS cholinergic neurons which are implicated in degenerative events associated with aging.
摘要
越来越多的证据表明,神经生长因子蛋白(NGF)作为一种用于外周和中枢神经系统(CNS)神经元的神经营养因子,可能在下丘脑 - 垂体 - 肾上腺皮质轴(HPAA)的调节中发挥作用。虽然应激暴露后啮齿动物中枢神经系统中的NGF结合减少,但通过用乙酰 - L - 肉碱(ALCAR)治疗可防止这种减少,乙酰 - L - 肉碱是一种能够预防一些与衰老相关的退行性事件的化学物质。2. 作者研究了冷应激对长期用ALCAR治疗的老年大鼠基底前脑和小脑中低亲和力NGF受体(p75NGFR)mRNA水平的影响。3. 目前的结果表明,ALCAR消除了老年动物基底前脑中与年龄相关的p75NGFR mRNA水平降低,但不影响对应激刺激的反应。4. 此外,用ALCAR治疗使老年动物小脑中的p75NGFR mRNA水平维持在几乎与年轻对照动物中观察到的水平相同的水平。5. 这些结果表明ALCAR对中枢胆碱能神经元具有神经保护作用,这种作用在p75NGFR转录水平发挥。p75NGFR水平的恢复可以增加这些中枢神经系统胆碱能神经元的NGF营养支持,这些神经元与衰老相关的退行性事件有关。