The prevalence of major depressive disorder (MDD) is higher in women than men. Importantly, a differential behavioral response by sex to the antidepressant response to ketamine in rodents has been reported. Mechanistically, male depressed-like animals showed an increased spine density after ketamine treatment via restoration of synaptic protein levels while those proteins were not altered in female rats. In addition, preclinical studies indicate that the impairment of astrocytic plasticity is one of the contributing mechanisms in the pathophysiology of MDD. Accordingly, in this study, we determined the effect of sex on the rapid morphological alteration of hippocampal astrocytes and the serum level of BDNF one hour after S-ketamine injection. A single intraperitoneal dose of S-ketamine (15 mg/kg) or saline was injected to the male and female Flinders Sensitive Line (FSL) rats, a genetic animal model of depression and their brains were perfused one hour after treatment. The size of the GFAP positive astrocytes in the hippocampal subregions was measured. The volume of different hippocampal subregions was assessed using the Cavalieri estimator. Moreover, serum levels of BDNF were measured with enzyme-linked immunosorbent assay (ELISA) kits. The volume of hippocampal subregions significantly increased one hour after S-ketamine in both male and female FSL animals. However, a substantial alteration in the morphology of the hippocampal astrocytes was observed only in the female rats. Additionally, significantly increased serum BDNF levels in the female depressed rats were observed one hour after S-ketamine treatment. Our results indicate that the rapid effects of S-ketamine on the morphology of the hippocampal astrocytes and the serum level of BDNF are sex-dependent.

中文翻译：

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S-氯胺酮对海马星形胶质细胞形态和BDNF血清水平的性别依赖性快速影响

女性重度抑郁症 (MDD) 的患病率高于男性。重要的是，已经报道了啮齿动物对氯胺酮的抗抑郁反应的不同性别行为反应。从机制上讲，雄性抑郁样动物在氯胺酮治疗后通过突触蛋白水平的恢复显示出脊柱密度增加，而雌性大鼠中这些蛋白质没有改变。此外，临床前研究表明，星形胶质细胞可塑性受损是 MDD 病理生理学的促成机制之一。因此，在本研究中，我们确定了性别对注射 S-氯胺酮后 1 小时海马星形胶质细胞快速形态学改变和 BDNF 血清水平的影响。对雄性和雌性 Flinders Sensitive Line (FSL) 大鼠、抑郁症遗传动物模型和它们的大脑注射单次腹腔内剂量的 S-氯胺酮 (15 mg/kg) 或生理盐水，治疗后一小时。测量了海马亚区中 GFAP 阳性星形胶质细胞的大小。使用 Cavalieri 估计器评估不同海马亚区的体积。此外，使用酶联免疫吸附测定 (ELISA) 试剂盒测量 BDNF 的血清水平。在雄性和雌性 FSL 动物中 S-氯胺酮后 1 小时，海马亚区的体积显着增加。然而，仅在雌性大鼠中观察到海马星形胶质细胞形态的实质性改变。此外，在 S-氯胺酮治疗后 1 小时，观察到雌性抑郁大鼠的血清 BDNF 水平显着增加。我们的结果表明 S-氯胺酮对海马星形胶质细胞形态和 BDNF 血清水平的快速影响具有性别依赖性。