Aims

Evidences suggest that hypobaric hypoxia (HH) exposure causes biochemical and molecular level perturbations in brain resulting to associated cognitive dysfunction. However, possible effect of HH on amygdala and the associated limbic regions (prefrontal cortex and hippocampus) based functions remains elusive. Regulated fear expression is essential for quick adaptations and optimal behavioral response. Therefore, the present study aims to investigate the effect of HH on biochemical and molecular mechanisms in amygdala along with the hippocampus and prefrontal cortex based fear memory.

Materials and methods

Adult male Sprague Dawley rats were subjected to cued and contextual fear memory assessment following simulated HH exposure (25,000 ft) for 3 and 7 days. Plasma and limbic tissue (Prefrontal cortex, hippocampus and amygdala) were collected for biochemical and molecular studies.

Key findings

Results revealed a decrement in contextual and cued fear memory retrieval, indicating to fear memory dysregulation under HH exposure. Increased level of norepinephrine, dopamine, corticosterone and glutamate along with a decline in serotonin and GABA level was observed in plasma, limbic tissue after 3 and 7 days of HH exposure. Dysregulation of neuromodulation, neuronal survival and synaptic homeostasis was also evident from observed decline in tryptophan hydroxylase, BDNF, synaptophysin, synapsin1, PSD95 and increase in tyrosine hydroxylase immunoreactivity in limbic region under HH exposure.

Significance

Dysregulation of limbic region's signaling molecules associated with survival and maintenance of synaptic plasticity (Synaptophysin, synapsin1 and PSD95), neurotrophic factor (BDNF) and shift in monoamines, corticosterone, glutamate and GABA basal levels may contribute to the HH induced fear memory impairment.

中文翻译：

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低压缺氧会削弱恐惧记忆：边缘区突触可塑性和神经调节剂的作用。

目的

有证据表明，低压缺氧（HH）暴露会导致大脑中的生化和分子水平紊乱，从而导致相关的认知功能障碍。然而，HH对杏仁核和相关边缘区域（前额叶皮层和海马）的功能可能产生的影响仍然难以捉摸。调节恐惧表达对于快速适应和最佳行为反应至关重要。因此，本研究旨在探讨HH对杏仁核以及基于海马和前额叶皮层的恐惧记忆的生化和分子机制的影响。

材料和方法

成年雄性Sprague Dawley大鼠在模拟的HH暴露（25,000 ft）下进行了3天和7天后，进行了暗示和情景恐惧记忆评估。收集血浆和边缘组织（前额叶皮层，海马和杏仁核）用于生化和分子研究。

主要发现

结果显示，在上下文和提示的恐惧记忆检索中递减，表明在HH暴露下恐惧记忆失调。暴露于HH 3天和7天后，血浆，边缘组织中的去甲肾上腺素，多巴胺，皮质酮和谷氨酸水平升高，同时血清素和GABA水平下降。在HH暴露下，观察到的色氨酸羟化酶，BDNF，突触素，synapsin1，PSD95的下降和酪氨酸羟化酶免疫反应性的增加，也明显证明了神经调节，神经元存活和突触稳态的失调。

意义

与生存和维持突触可塑性（突触素，synapsin1和PSD95），神经营养因子（BDNF）和单胺，皮质酮，谷氨酸和GABA的基础水平变化有关的边缘区域信号分子失调可能会导致HH诱发的恐惧记忆障碍。