Kumon Hiroshi, Yoshino Yuta, Funahashi Yu, Ochi Shinichiro, Iga Jun-Ichi, Ueno Shu-Ichi
Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
IBRO Neurosci Rep. 2023 Oct 2;15:281-286. doi: 10.1016/j.ibneur.2023.09.012. eCollection 2023 Dec.
Antipsychotic treatment is vital for patients with schizophrenia even in the perinatal period, but the impact at the molecular biological level on offspring is unclear. The aim of the present study was to investigate the effects of intraperitoneal haloperidol injection to pregnant mice on glutamate and GABA receptors in the brain of offspring mice. Eight-week-old pregnant mice were treated with either intraperitoneal haloperidol or normal saline injection, and their offspring were defined as F1 mice. In addition, eight-week-old male mice were used as acute mice that were intraperitoneally injected with haloperidol or normal saline for 20 days. mRNA expression levels were measured by RT-qPCR. Western blotting was performed of the frontal lobes of F1 mice. In the hippocampi of F1 mice, Grik3 (p = 0.023) and Gabra3 (p = 0.004) mRNA expression levels were significantly higher in the haloperidol group than in the control group, whereas Gria2 (p < 0.001) and Grin2a (p < 0.001) mRNA expression levels were significantly lower in the haloperidol group than in the control group. Gria2 (p = 0.015), and Grik3 (p = 0.037), and Grin2a (p = 0.012) mRNA expression levels were significantly lower in the haloperidol group than in the control group in the frontal lobes of F1 mice. In the hippocampi of acute mice, Grik3 (p = 0.049) and Gabra3 (p = 0.007) mRNA expression levels were significantly decreased in the haloperidol group. Fetal exposure to haloperidol can affect glutamate and GABA receptors through mRNA expression changes in the brain of offspring.
抗精神病药物治疗对精神分裂症患者至关重要，即使在围产期也是如此，但在分子生物学水平上对后代的影响尚不清楚。本研究的目的是探讨给怀孕小鼠腹腔注射氟哌啶醇对后代小鼠大脑中谷氨酸和GABA受体的影响。8周龄的怀孕小鼠接受腹腔注射氟哌啶醇或生理盐水治疗，其后代被定义为F1小鼠。此外，8周龄的雄性小鼠用作急性小鼠，腹腔注射氟哌啶醇或生理盐水20天。通过RT-qPCR测量mRNA表达水平。对F1小鼠的额叶进行蛋白质印迹分析。在F1小鼠的海马体中，氟哌啶醇组的Grik3（p = 0.023）和Gabra3（p = 0.004）mRNA表达水平显著高于对照组，而氟哌啶醇组的Gria2（p < 0.001）和Grin2a（p < 0.001）mRNA表达水平显著低于对照组。在F1小鼠额叶中，氟哌啶醇组的Gria2（p = 0.015）、Grik3（p = 0.037）和Grin2a（p = 0.012）mRNA表达水平显著低于对照组。在急性小鼠的海马体中，氟哌啶醇组的Grik3（p = 0.049）和Gabra3（p = 0.007）mRNA表达水平显著降低。胎儿期暴露于氟哌啶醇可通过后代大脑中mRNA表达的变化影响谷氨酸和GABA受体。
