Department of Neurobiology, Defence Institute of Physiology and Allied Sciences (DIPAS), Delhi, India.
PLoS One. 2013 May 21;8(5):e62235. doi: 10.1371/journal.pone.0062235. Print 2013.
Adverse environmental conditions such as hypobaric hypoxia (HH) cause memory impairment by affecting cellular machinery leading to neurodegeneration. Providing enriched environment (EE) is found to be beneficial for curing several neurodegenerative disorders. The protective role of EE in preventing HH induced neuronal death has been reported previously but the involved mechanism is still not clearly understood. The present study is an attempt to verify the impact of EE on spatial memory during HH and also to explore the possible role of neurotrophin in EE mediated neuroprotection. Signaling mechanism involved in neuroprotection was also explored. Male Sprague Dawley rats were simulated to HH condition in an Animal Decompression Chamber at an altitude of 25000 feet in standard and enriched cages for 7 days. Spatial memory was assessed through Morris Water Maze. Role of different neurotrophins was explored by gene silencing and inhibitors for their respective receptors. Further, using different blockers signaling pathway was also explored. Finding of the present study suggested that EE prevents HH mediated memory impairment and neurodegeneration. Also brain-derived neurotrophic factor (BDNF) plays a major role in EE mediated neuroprotection and it effectively prevented neurodegeneration by activating PI3K/AKT pathway resulting in GSK3β inactivation which further inhibits apoptosis. Moreover GSK3β phosphorylation and hence its inactivation upregulates CREB phosphorylation which may also accounts for activation of survival machinery in cells and provides neuroprotection. From these observations it can be postulated that EE has a therapeutic potential in amelioration of HH induced memory impairment and neurodegeneration. Hence it may be used as a non invasive and non pharmacological intervention against various neurological disorders.
不利的环境条件，如低气压缺氧（HH），通过影响细胞机制导致神经退行性病变，从而导致记忆障碍。研究发现，提供丰富的环境（EE）有益于治疗多种神经退行性疾病。EE 预防 HH 诱导的神经元死亡的保护作用以前已有报道，但涉及的机制仍不清楚。本研究试图验证 EE 在 HH 期间对空间记忆的影响，并探索神经营养因子在 EE 介导的神经保护中的可能作用。还探讨了参与神经保护的信号机制。雄性 Sprague Dawley 大鼠在动物减压室中模拟在海拔 25000 英尺的高度下的 HH 条件，在标准和丰富的笼子中进行 7 天。通过 Morris 水迷宫评估空间记忆。通过基因沉默和针对其各自受体的抑制剂来探索不同神经营养因子的作用。此外，还使用不同的阻断剂来探索信号通路。本研究的结果表明，EE 可预防 HH 介导的记忆障碍和神经退行性变。脑源性神经营养因子（BDNF）在 EE 介导的神经保护中起主要作用，它通过激活 PI3K/AKT 通路有效预防神经退行性变，从而使 GSK3β失活，进而抑制细胞凋亡。此外，GSK3β的磷酸化及其失活上调了 CREB 的磷酸化，这也可能是细胞存活机制的激活，并提供神经保护。从这些观察结果可以推断，EE 在改善 HH 诱导的记忆障碍和神经退行性变方面具有治疗潜力。因此，它可以用作治疗各种神经疾病的非侵入性和非药物干预措施。
