Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin 682022, Kerala, India.
Neurochem Res. 2012 Mar;37(3):629-38. doi: 10.1007/s11064-011-0654-4. Epub 2011 Nov 17.
Hypoxia in neonates disrupts the oxygen flow to the brain, essentially starving the brain and preventing it from performing vital biochemical processes important for central nervous system development. Hypoxia results in a permanent brain damage by gene and receptor level alterations mediated through neurotransmitters. The present study evaluated GABA, GABAA, GABAB receptor functions and gene expression changes in glutamate decarboxylase in the corpus striatum of hypoxic neonatal rats and the treatment groups with glucose, oxygen and epinephrine. Since GABA is the principal neurotransmitter involved in hypoxic ventilatory decline, the alterations in its level under hypoxic stress points to an important aspect of respiratory control. Following hypoxic stress, a significant decrease in total GABA, GABAA and GABAB receptors function and GAD expression was observed in the striatum, which accounts for the ventilator decline. Hypoxic rats treated with glucose alone and with oxygen showed a reversal of the receptor alterations and changes in GAD to near control. Being a source of immediate energy, glucose can reduce the ATP-depletion-induced changes in GABA and oxygenation helps in overcoming reduction in oxygen supply. Treatment with oxygen alone and epinephrine was not effective in reversing the altered receptor functions. Thus, our study point to the functional role of GABA receptors in mediating ventilatory response to hypoxia and the neuroprotective role of glucose treatment. This has immense significance in the proper management of neonatal hypoxia for a better intellect in the later stages of life.
新生儿缺氧会干扰大脑的氧气供应，实质上是使大脑饥饿，并阻止其进行对中枢神经系统发育至关重要的重要生化过程。缺氧通过神经递质介导的基因和受体水平改变导致永久性脑损伤。本研究评估了缺氧新生大鼠纹状体中 GABA、GABAA 和 GABAB 受体功能以及谷氨酸脱羧酶基因表达的变化，以及葡萄糖、氧气和肾上腺素治疗组的变化。由于 GABA 是参与缺氧性通气下降的主要神经递质，因此在缺氧应激下其水平的改变指出了呼吸控制的一个重要方面。缺氧应激后，纹状体中总 GABA、GABAA 和 GABAB 受体功能以及 GAD 表达显著下降，这是通气下降的原因。单独用葡萄糖和用氧气治疗的缺氧大鼠表现出受体改变和 GAD 向接近对照的逆转。葡萄糖作为即时能量的来源，可以减少由 ATP 耗竭引起的 GABA 变化，而氧合有助于克服氧气供应减少。单独用氧气和肾上腺素治疗不能有效逆转改变的受体功能。因此，我们的研究表明 GABA 受体在介导对缺氧的通气反应中具有功能作用，葡萄糖治疗具有神经保护作用。这对于新生儿缺氧的正确管理具有重要意义，可在生命后期获得更好的智力。
