Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon 791-0295, Japan.
Department of Pediatrics, Graduate School of Medicine, Ehime University, Toon 791-0295, Japan.
Cells. 2022 Nov 17;11(22):3649. doi: 10.3390/cells11223649.
In addition to genetic factors, environmental factors play a role in the pathogenesis of attention deficit/hyperactivity disorder (ADHD). This study used Lister hooded rats (LHRs) as ADHD model animals to evaluate the effects of environmental factors. Male LHR pups were kept in four rearing conditions from postnatal day 23 (4 rats in a standard cage; 12 rats in a large flat cage; and 4 or 12 rats in an enriched environment [EE]) until 9 weeks of age. EE rearing but not rearing in a large flat cage decreased the activity of LHRs in the open field test that was conducted for 7 consecutive days. In the drop test, most rats reared in an EE remained on a disk at a height, whereas most rats reared in a standard cage fell off. RNA sequencing revealed that the immediate-early gene expression in the medial prefrontal cortex of LHRs reared in an EE was reduced. cFos-expressing neurons were reduced in number in LHRs reared in an EE. These results suggest that growing in an EE improves ADHD-like behaviors and that said improvement is due to the suppression of neuronal activity in the mPFC.
除了遗传因素,环境因素在注意缺陷多动障碍(ADHD)的发病机制中也起着作用。本研究使用 Lister 封闭群大鼠(LHRs)作为 ADHD 模型动物来评估环境因素的影响。雄性 LHR 幼仔从出生后第 23 天(4 只大鼠在标准笼中;12 只大鼠在大平笼中;4 只或 12 只大鼠在丰富环境[EE]中)开始,一直饲养到 9 周龄。EE 饲养但不在大平笼中饲养可降低 LHR 在连续 7 天进行的旷场试验中的活动度。在跌落试验中,大多数在 EE 中饲养的大鼠留在高处的圆盘上,而大多数在标准笼中饲养的大鼠则掉落。RNA 测序显示,在 EE 中饲养的 LHR 中内侧前额叶皮质的即刻早期基因表达减少。在 EE 中饲养的 LHR 中 cFos 表达神经元的数量减少。这些结果表明,在 EE 中生长可以改善类似 ADHD 的行为,而这种改善是由于 mPFC 中神经元活性的抑制。