脑活素对老龄大鼠脑内神经生长因子系统的影响。
Effects of cerebrolysin on nerve growth factor system in the aging rat brain.
作者信息
Stepanichev Mikhail, Onufriev Mikhail, Aniol Viktor, Freiman Sofia, Brandstaetter Hemma, Winter Stefan, Lazareva Natalia, Guekht Alla, Gulyaeva Natalia
机构信息
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia.
Moscow State Budgetary Health Institution "Moscow Research and Clinical Center for Neuropsychiatry" of the Healthcare Department of Moscow, Russia.
出版信息
Restor Neurol Neurosci. 2017;35(6):571-581. doi: 10.3233/RNN-170724.
BACKGROUND
Aging is associated with some cognitive decline and enhanced risk of development of neurodegenerative diseases. It is assumed that altered metabolism and functions of neurotrophin systems may underlie these age-related functional and structural modifications. CerebrolysinTM (CBL) is a neuropeptide mixture with neurotrophic effects, which is widely used for the treatment of stroke and traumatic brain injury patients. It is also evident that CBL has an overall beneficial effect and a favorable benefit-risk ratio in patients with dementia. However, the effects of CBL on cognition and brain neurotrophin system in normal aging remain obscure.
OBJECTIVE
The aim of the present study was to examine the age-related modifications of endogenous neurotrophin systems in the brain of male Wistar rats and the effects of CBL on learning and memory as well as the levels neurotrophins and their receptors.
METHODS
Old (23-24 months) and young (2-3 months) male Wistar rats were used for the study. A half of animals were subjected to CBL course (2.5 ml/kg, 20 i.p. injections). Behavior of rats was studied using the open field test and simple water maze training. The contents of NGF and BDNF were studied using enzyme-linked immunosorbent assay; the expression of neurotrophin receptors was estimated by Western-blot analysis.
RESULTS
CBL treatment did not affect general status, age-related weight changes, general locomotor activity as well as general brain histology. In a water maze task, a minor effect of CBL was observed in old rats at the start of training and no effect on memory retention was found. Aging induced a decrease in neurotrophin receptors TrkA, TrkB, and p75NTR in the neocortex. CBL counteracted effects of aging on neocortical TrkA and p75NTR receptors and decreased expression of proNGF without influencing overall NGF levels. BDNF system was not significantly affected by CBL.
CONCLUSION
The pro-neuroplastic "antiaging" effects of CBL in the neocortex of old animals were generally related to the NGF rather than the BDNF system.
背景
衰老与一些认知能力下降以及神经退行性疾病发生风险增加相关。据推测，神经营养因子系统代谢和功能的改变可能是这些与年龄相关的功能和结构改变的基础。脑蛋白水解物（CBL）是一种具有神经营养作用的神经肽混合物，广泛用于治疗中风和创伤性脑损伤患者。同样明显的是，CBL对痴呆患者具有总体有益作用且效益风险比良好。然而，CBL对正常衰老过程中认知和脑神经营养因子系统的影响仍不清楚。
目的
本研究旨在探讨雄性Wistar大鼠脑内内源性神经营养因子系统与年龄相关的改变，以及CBL对学习和记忆以及神经营养因子及其受体水平的影响。
方法
选用老年（23 - 24个月）和年轻（2 - 3个月）雄性Wistar大鼠进行研究。一半动物接受CBL疗程（2.5 ml/kg，腹腔注射20次）。使用旷场试验和简单水迷宫训练研究大鼠行为。采用酶联免疫吸附测定法研究NGF和BDNF含量；通过蛋白质印迹分析评估神经营养因子受体的表达。
结果
CBL治疗不影响一般状态、与年龄相关的体重变化、一般运动活动以及一般脑组织结构。在水迷宫任务中，训练开始时在老年大鼠中观察到CBL有轻微作用，且对记忆保持无影响。衰老导致新皮质中神经营养因子受体TrkA、TrkB和p75NTR减少。CBL抵消了衰老对新皮质TrkA和p75NTR受体的影响，并降低了前体NGF的表达，而不影响总体NGF水平。BDNF系统未受到CBL的显著影响。
结论
CBL在老年动物新皮质中的促神经可塑性“抗衰老”作用通常与NGF系统而非BDNF系统有关。
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