Titus A D J, Shankaranarayana Rao B S, Harsha H N, Ramkumar K, Srikumar B N, Singh S B, Chattarji S, Raju T R
Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, PB # 2900, Hosur Road, Bangalore 560029, India.
Neuroscience. 2007 Mar 2;145(1):265-78. doi: 10.1016/j.neuroscience.2006.11.037. Epub 2007 Jan 12.
Simulated hypobaric hypoxia (HBH), resembling high altitude hypoxia severely affects the CNS and results in several physiological changes. The hippocampus is closely associated with learning and memory and an insult to this region affects cognition. Previous studies suggest that rapid or prolonged exposures to HBH are associated with psychomotor and cognitive impairments. The defense personnel, mountain climbers and rescue teams are exposed to such harsh environment and thus it demands a systematic study emphasizing the subtle effects of such extreme environments on cognitive function. Accordingly, this study evaluated the effect of hypobaric hypoxia on structural changes in the principal neurons of the hippocampus and learning in eight-arm radial maze. Adult male Wistar rats, subjected to simulated hypobaric hypoxia equivalent to an altitude of 6000 m for a period of 2 or 7 days, in a hypoxic chamber served as hypoxic group (HY). Rats housed in a similar chamber for the same period of time, without hypoxic exposure served as sham control (SC), while normal control (NC) group of rats were housed in standard laboratory conditions. The dendritic morphology of neurons in cornu ammonis region 1 (CA1) and cornu ammonis region 3 (CA3) was studied in Golgi-impregnated hippocampal sections. Exposure for 2 days to hypobaric hypoxia had minimal deleterious effects on the CA1 pyramidal neurons, while exposure for 7 days resulted in a significant decrease in the number of branching points, intersections and dendritic length. Unlike the CA1 pyramidal neurons, the CA3 neurons exhibited dendritic atrophy following both 2 and 7 days of hypoxic exposure. Further, hippocampal-dependent spatial learning was affected marginally following 2 day exposure, while 7 day exposure severely affected learning of the partially baited radial arm maze task. Our study suggests that dendritic atrophy in the hippocampus on exposure to HBH could be one of the bases for the cognitive deficits exhibited under such conditions.
模拟低压缺氧（HBH），类似于高原缺氧，会严重影响中枢神经系统并导致多种生理变化。海马体与学习和记忆密切相关，该区域受损会影响认知。先前的研究表明，快速或长时间暴露于HBH会导致精神运动和认知障碍。国防人员、登山者和救援队会暴露于这种恶劣环境中，因此需要进行系统研究，以强调这种极端环境对认知功能的细微影响。因此，本研究评估了低压缺氧对海马体主要神经元结构变化以及八臂放射状迷宫学习能力的影响。成年雄性Wistar大鼠，在缺氧舱中暴露于相当于海拔6000米的模拟低压缺氧环境2天或7天，作为缺氧组（HY）。在相同时间段内饲养在类似舱室中但未暴露于缺氧环境的大鼠作为假对照组（SC），而正常对照组（NC）的大鼠饲养在标准实验室条件下。在高尔基染色的海马体切片中研究了海马体1区（CA1）和海马体3区（CA3）神经元的树突形态。暴露于低压缺氧2天对CA1锥体神经元的有害影响最小，而暴露7天则导致分支点、交叉点数量和树突长度显著减少。与CA1锥体神经元不同，CA3神经元在缺氧暴露2天和7天后均表现出树突萎缩。此外，暴露2天后，海马体依赖的空间学习受到轻微影响，而暴露7天则严重影响部分诱饵放射状臂迷宫任务的学习。我们的研究表明，暴露于HBH时海马体中的树突萎缩可能是在这种情况下出现认知缺陷的基础之一。
