Mocchetti Italo, Bachis Alessia, Campbell Lee A, Avdoshina Valeriya
Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, WP13 New Research Building, 3970 Reservoir Rd, NW, Washington, DC, 20057, USA,
J Neuroimmune Pharmacol. 2014 Mar;9(2):80-91. doi: 10.1007/s11481-013-9488-y. Epub 2013 Jul 6.
Human immunodeficiency virus type-1 (HIV) causes mild or severe neurological problems, termed HIV-associated neurocognitive disorder (HAND), even when HIV patients receive antiretroviral therapy. Thus, novel adjunctive therapies are necessary to reduce or abolish the neurotoxic effect of HIV. However, new therapies require a better understanding of the molecular and cellular mechanisms of HIV-induced neurotoxicity. HAND subjects are characterized by being profoundly depressed, and they experience deficits in memory, learning and movements. Experimental evidence has also shown that HIV reduces neurogenesis. These deficits resemble those occurring in premature brain aging or in a brain with impaired neural repair properties. Thus, it appears that HIV diminishes neuronal survival, along with reduced neuronal connections. These two phenomena should not occur in the adult and developing brain when synaptic plasticity is promoted by neurotrophic factors, polypeptides that are present in adult synapses. This review will outline experimental evidence as well as present emerging concepts for the use of neurotrophic factors and in particular brain-derived neurotrophic factor as an adjunct therapy to prevent HIV-mediated neuronal degeneration and restore the loss of synaptic connections.
1型人类免疫缺陷病毒（HIV）会引发轻度或重度神经问题，即所谓的HIV相关神经认知障碍（HAND），即便HIV患者接受了抗逆转录病毒治疗也是如此。因此，需要新的辅助疗法来减轻或消除HIV的神经毒性作用。然而，新疗法需要更好地理解HIV诱导神经毒性的分子和细胞机制。HAND患者的特征是极度抑郁，且存在记忆、学习和运动方面的缺陷。实验证据还表明，HIV会减少神经发生。这些缺陷类似于过早脑衰老或神经修复特性受损的大脑中出现的缺陷。因此，似乎HIV会减少神经元存活，同时减少神经元连接。当神经营养因子（存在于成人突触中的多肽）促进突触可塑性时，这两种现象在成人大脑和发育中的大脑中不应出现。本综述将概述实验证据，并介绍使用神经营养因子，特别是脑源性神经营养因子作为辅助疗法来预防HIV介导的神经元变性和恢复突触连接丧失的新观念。
