Irie Kanako, Ohta Ken-Ichi, Ujihara Hidetoshi, Araki Chihiro, Honda Kodai, Suzuki Shingo, Warita Katsuhiko, Otabi Hikari, Kumei Haruki, Nakamura Shinji, Koyano Kosuke, Miki Takanori, Kusaka Takashi
Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Department of Pediatrics, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Front Neurosci. 2024 Jan 16;17:1308368. doi: 10.3389/fnins.2023.1308368. eCollection 2023.
Early child maltreatment, such as child abuse and neglect, is well known to affect the development of social skills. However, the mechanisms by which such an adverse environment interrupts the development of social skills remain unelucidated. Identifying the period and brain regions that are susceptible to adverse environments can lead to appropriate developmental care later in life. We recently reported an excitatory/inhibitory imbalance and low activity during social behavior in the medial prefrontal cortex (mPFC) of the maternal separation (MS) animal model of early life neglect after maturation. Based on these results, in the present study, we investigated how MS disturbs factors related to excitatory and inhibitory neurons in the mPFC until the critical period of mPFC development. Additionally, we evaluated whether the effects of MS could be recovered in an enriched environment after MS exposure. Rat pups were separated from their dams on postnatal days (PDs) 2-20 (twice daily, 3 h each) and compared with the mother-reared control (MRC) group. Gene expression analysis revealed that various factors related to excitatory and inhibitory neurons were transiently disturbed in the mPFC during MS. A similar tendency was found in the sensory cortex; however, decreased parvalbumin (PV) expression persisted until PD 35 only in the mPFC. Moreover, the number of PV interneurons decreased in the ventromedial prefrontal cortex (vmPFC) on PD 35 in the MS group. Additionally, perineural net formation surrounding PV interneurons, which is an indicator of maturity and critical period closure, was unchanged, indicating that the decreased PV interneurons were not simply attributable to developmental delay. This reduction of PV interneurons improved to the level observed in the MRC group by the enriched environment from PD 21 after the MS period. These results suggest that an early adverse environment disturbs the development of the mPFC but that these abnormalities allow room for recovery depending on the subsequent environment. Considering that PV interneurons in the mPFC play an important role in social skills such as empathy, an early rearing environment is likely a very important factor in the subsequent acquisition of social skills.
众所周知，早期儿童虐待，如虐待和忽视儿童，会影响社交技能的发展。然而，这种不利环境干扰社交技能发展的机制仍未阐明。确定易受不利环境影响的时期和脑区，有助于在日后生活中提供适当的发育护理。我们最近报道，在早期生活忽视的母体分离（MS）动物模型成熟后，内侧前额叶皮质（mPFC）在社交行为期间存在兴奋/抑制失衡和低活性。基于这些结果，在本研究中，我们调查了MS如何在mPFC发育的关键期之前干扰与兴奋性和抑制性神经元相关的因素。此外，我们评估了MS暴露后，丰富环境是否能恢复MS的影响。将出生后第2 - 20天（每天两次，每次3小时）的幼鼠与母鼠饲养的对照组（MRC）分开，并进行比较。基因表达分析显示，在MS期间，mPFC中与兴奋性和抑制性神经元相关的各种因素受到短暂干扰。感觉皮层也发现了类似的趋势；然而，仅在mPFC中，小白蛋白（PV）表达的降低持续到出生后第35天。此外，MS组在出生后第35天，腹内侧前额叶皮质（vmPFC）中的PV中间神经元数量减少。此外，围绕PV中间神经元的神经周网形成，这是成熟和关键期关闭的指标，没有变化，表明PV中间神经元的减少并非仅仅归因于发育延迟。在MS期后的出生后第21天开始，通过丰富环境，PV中间神经元的这种减少改善到了MRC组观察到的水平。这些结果表明，早期不利环境会干扰mPFC的发育，但这些异常情况根据后续环境有恢复的空间。考虑到mPFC中的PV中间神经元在诸如同理心等社交技能中起重要作用，早期饲养环境可能是随后获得社交技能的一个非常重要的因素。
