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母体剥夺引起的早期生活应激影响成年雄性小鼠新皮质中间神经元的树突形态。

Early-Life Stress Caused by Maternal Deprivation Impacts Dendritic Morphology of Adult Male Mouse Neocortical Interneurons.

作者信息

Nakhal Mohammed M, Yassin Lidya K, Al Houqani Shaikha, Mydeen Ayishal B, Ibrahim Marwa F, Shehab Safa, Allouh Mohammed Z, Hamad Mohammad I K

机构信息

Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates.

出版信息

Int J Mol Sci. 2025 Feb 23;26(5):1909. doi: 10.3390/ijms26051909.

Abstract

A substantial body of research suggests that early-life stress (ELS) is associated with neuropathology in adulthood. Maternal deprivation (MD) is a commonly utilised model in mice for the study of specific neurological diseases. The appropriate growth of dendrites is essential for the optimal functioning of the nervous system. However, the impact of ELS on interneuron dendritic morphology remains unclear. To ascertain whether ELS induces alterations in the morphology of GABAergic inhibitory interneurons in layers II/III of the medial entorhinal cortex (mEC), the somatosensory cortex (SSC), the motor cortex (MC), and the CA1 region of the hippocampus (Hp), 9-day-old male GAD-67-EGFP transgenic mice were subjected to a 24 h MD. At postnatal day 60 (P60), the animals were sacrificed, and their brains were subjected to morphological analyses. The results indicated that MD affected the dendritic morphology of GABAergic interneurons. The mean dendritic length and mean dendritic segments of the examined cortical areas, except for the MC, were significantly decreased, whereas the number of primary dendrites was unaffected. Furthermore, the density of GAD67-EGFP-positive interneurons was decreased in the mEC and Hp, but not in the somatosensory and MC. The induction of ELS through MD in a developmental time window when significant morphological changes occur rendered the developing cells particularly susceptible to stress, resulting in a significant reduction in the number of surviving interneurons at the adult stage.

摘要

大量研究表明,早期生活应激(ELS)与成年期神经病理学有关。母体剥夺(MD)是小鼠中常用的一种模型,用于研究特定的神经疾病。树突的适当生长对于神经系统的最佳功能至关重要。然而,ELS对中间神经元树突形态的影响仍不清楚。为了确定ELS是否会诱导内嗅皮质(mEC)、躯体感觉皮质(SSC)、运动皮质(MC)和海马体(Hp)CA1区II/III层中GABA能抑制性中间神经元的形态改变,对9日龄雄性GAD-67-EGFP转基因小鼠进行了24小时的MD处理。在出生后第60天(P60),处死动物,并对其大脑进行形态学分析。结果表明,MD影响了GABA能中间神经元的树突形态。除MC外,所检查皮质区域的平均树突长度和平均树突节段显著减少,而初级树突的数量未受影响。此外,mEC和Hp中GAD67-EGFP阳性中间神经元的密度降低,但躯体感觉皮质和MC中未降低。在发生显著形态变化的发育时间窗口通过MD诱导ELS,使发育中的细胞特别容易受到应激影响,导致成年期存活中间神经元的数量显著减少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c00f/11900613/4adf1a4b8fde/ijms-26-01909-g001.jpg

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