Suwaluk Arbthip, Chutabhakdikul Nuanchan
Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73130, Thailand.
Brain Sci. 2022 Jul 31;12(8):1015. doi: 10.3390/brainsci12081015.
Maternal stress can afflict fetal brain development, putting the offspring at risk of cognitive deficits, including anxiety. The prefrontal cortex (PFC), a protracted maturing region, is notably affected by prenatal stress (PS). However, it remains unclear how PS interferes with the maturation of the GABAergic system, considering its functional adjustment in the PFC during adolescence. The present study thus investigated the long-lasting consequences of PS on the prefrontal GABAergic functions of adolescent offspring. Pregnant Sprague-Dawley rats were divided into controls and the PS group, which underwent restraint stress during the last week of gestation. Male pups from postnatal days (PND) 40-42 were submitted to the elevated plus maze (EPM) test. Proteins essentially involved in GABAergic signaling were then examined in PFC tissues, including the K-Cl cotransporter (KCC2), Na-K-Cl cotransporter (NKCC1), α1 and α5 subunits of GABA type A receptors (GABA receptors), and parvalbumin (PV), along with cAMP response element-binding protein phosphorylation (pCREB), which reacts in the plasticity regulation of PV-positive interneurons. The results revealed that the higher anxiety-like behavior of PS adolescent rats concurred with the significant decreases of the KCC2 and α1 subunits, with PV- and pCREB-lowered levels. The findings suggested that PS disrupts the continuance of PFC maturity by reducing the essential elements of GABAergic functions. These changes likely underlie the anxiety emerging in adolescence, possibly progressing to mental disorders.
母体压力会影响胎儿大脑发育，使后代面临认知缺陷的风险，包括焦虑。前额叶皮质（PFC）是一个发育过程较长的区域，尤其容易受到产前应激（PS）的影响。然而，考虑到其在青春期PFC中的功能调整，PS如何干扰GABA能系统的成熟仍不清楚。因此，本研究调查了PS对青春期后代前额叶GABA能功能的长期影响。将怀孕的Sprague-Dawley大鼠分为对照组和PS组，PS组在妊娠最后一周接受束缚应激。对出生后第40 - 42天的雄性幼崽进行高架十字迷宫（EPM）测试。然后检测PFC组织中与GABA能信号传导基本相关的蛋白质，包括钾氯共转运体（KCC2）、钠钾氯共转运体（NKCC1）、A型GABA受体（GABA受体）的α1和α5亚基以及小白蛋白（PV），以及在PV阳性中间神经元可塑性调节中起反应的环磷酸腺苷反应元件结合蛋白磷酸化（pCREB）。结果显示，PS青春期大鼠较高的焦虑样行为与KCC2和α1亚基的显著减少以及PV和pCREB水平的降低相一致。研究结果表明，PS通过减少GABA能功能的基本要素破坏了PFC成熟的持续性。这些变化可能是青春期出现焦虑的基础，甚至可能发展为精神障碍。
