Nejatbakhsh Mehrdad, Saboory Ehsan, Bagheri Morteza
Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran; Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran.
Int J Dev Neurosci. 2018 Aug;68:66-71. doi: 10.1016/j.ijdevneu.2018.05.003. Epub 2018 May 11.
The GABAergic synapses go through structural and functional maturation during early brain development. Maternal stress alters GABAergic synapses in developing brain, which are associated with the pathophysiology of neuropsychiatric disorders in adults. The present study aimed to investigate the effect of prenatal restraint stress (PS) on pilocarpine-induced seizure and ɑ5 subunit of γ-amino butyric acid type A (GABA) receptor expression in hippocampus. Pregnant Wistar rats were subjected to PS at gestational days 15-17 and the pups were examined for susceptibility to seizure and ɑ5 subunit of GABA receptor expression in hippocampus at postnatal days 14 and 21 (P14 and PND 21). Quantitative real-time PCR was used for evaluating the gene expression in the pups. Pilocarpine was injected intraperitoneally into the pups and seizure behaviors were recorded. The results showed that ɑ5 subunit mRNA expression significantly increased in hippocampus at both the P14 and P21 in the stressed rats. However, ɑ5 subunit level was greater at the P21 than at the P14 in both the groups. Latency of first tonic-clonic seizure significantly decreased in the PS group compared to the control pups. Number and duration of tonic-clonic seizures increased in the PS rats compared to the controls. PS led to an increase in total score of seizure at the P14 and P21. It can be concluded that PS increases the seizure susceptibility and GABA receptor ɑ5 subunit gene expression in offspring; it is likely that the mechanism of increased seizure susceptibility by PS, at least in part, can increase the GABA receptor ɑ5 subunit gene expression in hippocampus.
γ-氨基丁酸能突触在脑发育早期经历结构和功能成熟。母体应激会改变发育中脑内的γ-氨基丁酸能突触，这与成人神经精神疾病的病理生理学相关。本研究旨在探讨产前束缚应激（PS）对毛果芸香碱诱导的癫痫发作以及海马中γ-氨基丁酸A型（GABA）受体α5亚基表达的影响。将怀孕的Wistar大鼠在妊娠第15 - 17天施加PS，在出生后第14天和第21天（P14和PND 21）检查幼崽对癫痫发作的易感性以及海马中GABA受体α5亚基的表达。采用定量实时PCR评估幼崽中的基因表达。向幼崽腹腔注射毛果芸香碱并记录癫痫发作行为。结果显示，应激大鼠在P14和P21时海马中α5亚基mRNA表达均显著增加。然而，两组中P21时的α5亚基水平均高于P14时。与对照幼崽相比，PS组首次强直阵挛性发作的潜伏期显著缩短。与对照组相比，PS大鼠的强直阵挛性发作次数和持续时间增加。PS导致P14和P21时癫痫发作总分增加。可以得出结论，PS增加了后代的癫痫易感性和GABA受体α5亚基基因表达；PS增加癫痫易感性的机制，至少部分原因，可能是增加了海马中GABA受体α5亚基基因表达。
