Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Brain Behav. 2023 May;13(5):e2986. doi: 10.1002/brb3.2986. Epub 2023 Apr 9.
In the study, we examined the effects of ketamine and extremely low-frequency electromagnetic fields (ELF-EMF) on depression-like behavior, learning and memory, expression of GFAP, caspase-3, p53, BDNF, and NMDA receptor in animals subjected to chronic unpredictable stress (CUS).
After applying 21 days of chronic unpredictable stress, male rats received intraperitoneal (IP) of ketamine (5 mg/kg) and then were exposed to ELF-EMF (10-Hz, 10-mT exposure conditions) for 3 days (3 h per day) and behavioral assessments were performed 24 h after the treatments. Instantly after the last behavioral test, the brain was extracted for Nissl staining, immunohistochemistry, and real-time PCR analyses. Immunohistochemistry (IHC) was conducted to assess the effect of ketamine and ELF-EMF on the expression of astrocyte marker (glial fibrillary acidic protein, GFAP) in the CA1 area of the hippocampus and medial prefrontal cortex (mPFC). Also, real-time PCR analyses were used to investigate the impacts of the combination of ketamine and ELF-EMF on the expression of caspase3, p53, BDNF, and NMDA receptors in the hippocampus in rats submitted to the CUS procedure. Results were considered statistically significant when p < .05.
Our results revealed that the combination of ketamine and ELF-EMF increased depression-like behavior, increased degenerated neurons and decreased the number of GFAP (+) cells in the CA1 area and mPFC, incremented the expression of caspase-3, and reduced the expression of BDNF in the hippocampus but showed no effect on the expression of p53 and NMDA-R.
These results reveal that combining ketamine and ELF-EMF has adverse effects on animals under chronic unpredictable stress (CUS).
在这项研究中，我们研究了氯胺酮和极低频电磁场（ELF-EMF）对经历慢性不可预测应激（CUS）的动物的抑郁样行为、学习和记忆、GFAP、caspase-3、p53、BDNF 和 NMDA 受体表达的影响。
在应用 21 天慢性不可预测应激后，雄性大鼠接受腹腔内（IP）注射氯胺酮（5mg/kg），然后暴露于 ELF-EMF（10-Hz、10-mT 暴露条件）3 天（每天 3 小时），并在治疗后 24 小时进行行为评估。在最后一次行为测试后立即提取大脑进行尼氏染色、免疫组织化学和实时 PCR 分析。免疫组织化学（IHC）用于评估氯胺酮和 ELF-EMF 对海马 CA1 区和内侧前额叶皮质（mPFC）中星形胶质细胞标志物（胶质纤维酸性蛋白，GFAP）表达的影响。此外，实时 PCR 分析用于研究氯胺酮和 ELF-EMF 联合对接受 CUS 程序的大鼠海马中 caspase3、p53、BDNF 和 NMDA 受体表达的影响。当 p<.05 时，结果被认为具有统计学意义。
我们的结果表明，氯胺酮和 ELF-EMF 的联合使用增加了抑郁样行为，增加了退化神经元，减少了 CA1 区和 mPFC 中 GFAP（+）细胞的数量，增加了 caspase-3 的表达，减少了海马中 BDNF 的表达，但对 p53 和 NMDA-R 的表达没有影响。
这些结果表明，氯胺酮和 ELF-EMF 的联合使用对慢性不可预测应激（CUS）下的动物有不良影响。
