Essential role of microglia in the fast antidepressant action of ketamine and hypidone hydrochloride (YL-0919).

Introduction: Intracerebral microglia play a vital role in mediating central immune response, neuronal repair and synaptic pruning, but its precise role and mechanism in fast action of antidepressants have remained unknown. In this study, we identified that the microglia contributed to the rapid action of antidepressants ketamine and YL-0919. Methods: The depletion of microglia was achieved with the diet containing the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 in mice. The tail suspension test (TST), forced swimming test (FST) and novelty suppressed feeding test (NSFT) were employed to evaluate the rapid acting antidepressant behavior of ketamine and YL-0919 in the microglia depletion model. The number of microglia in the prefrontal cortex (PFC) was assayed by the immunofluorescence staining. The expressions of synaptic proteins (synapsin-1, PSD-95, GluA1) and brain-derived neurotrophic factor (BDNF) in the PFC were tested by Western blot. Results: The immobility duration in FST and the latency to feed in NSFT were shortened 24 h after an intraperitoneal (i.p.) injection of ketamine (10 mg/kg). The microglial depletion of PLX3397 blocked the rapid antidepressant-like effect of ketamine in mice. In addition, the immobility time in TST and FST as well as latency to feed in NSFT were reduced 24 h after the intragastric (i.g.) administration of YL-0919 (2.5 mg/kg), and the rapid antidepressant effect of YL-0919 was also blocked by the microglial depletion using PLX5622. About 92% of microglia in the prefrontal cortex was depleted in PLX5622 diet-fed mice, while both ketamine and YL-0919 promoted proliferation on the remaining microglia. YL-0919 significantly increased the protein expressions of synapsin-1, PSD-95, GluA1 and BDNF in the PFC, all of which could be blocked by PLX5622. Conclusion: These results suggested the microglia underlying the rapid antidepressant-like effect of ketamine and YL-0919, and microglia would likely constitute in the rapid enhancing impact of synaptic plasticity in the prefrontal cortex by YL-0919.

Corrigendum: Essential role of microglia in the fast antidepressant action of ketamine and hypidone hydrochloride (YL-0919).

[This corrects the article DOI: 10.3389/fphar.2023.1122541.].

Astrocytes underlie a faster-onset antidepressant effect of hypidone hydrochloride (YL-0919).

Introduction: Major depression disorder (MDD) is a common and potentially life-threatening mental illness; however, data on its pathogenesis and effective therapeutic measures are lacking. Pathological changes in astrocytes play a pivotal role in MDD. While hypidone hydrochloride (YL-0919), an independently developed antidepressant, has shown rapid action with low side effects, its underlying astrocyte-specific mechanisms remain unclear. Methods: In our study, mice were exposed to chronic restraint stress (CRS) for 14 days or concomitantly administered YL-0919/fluoxetine. Behavioral tests were applied to evaluate the depression model; immunofluorescence and immunohistochemistry staining were used to explore morphological changes in astrocytes; astrocyte-specific RNA sequencing (RNA-Seq) analysis was performed to capture transcriptome wide alterations; and ATP and oxygen consumption rate (OCR) levels of primary astrocytes were measured, followed by YL-0919 incubation to appraise the alteration of energy metabolism and mitochondrial oxidative phosphorylation (OXPHOS). Results: YL-0919 alleviated CRS-induced depressive-like behaviors faster than fluoxetine and attenuated the number and morphologic deficits in the astrocytes of depressed mice. The changes of gene expression profile in astrocytes after CRS were partially reversed by YL-0919. Moreover, YL-0919 improved astrocyte energy metabolism and mitochondrial OXPHOS in astrocytes. Conclusion: Our results provide evidence that YL-0919 exerted a faster-onset antidepressant effect on CRS-mice possibly via astrocyte structural remodeling and mitochondria functional restoration.

Infection of Chlamydia trachomatis and apoptosis of spermatogenic cells / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between infection of Chlamydia Trachomatis(Ct) and apoptosis of spermatogenic cells.</p><p><b>METHODS</b>Apoptotic spermatogenic cells were examined by Wright-Giemsa staining and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate(dUTP)-biotin nick-end labeling(TUNEL) technique.</p><p><b>RESULTS</b>Apoptosis rate of Ct infective group was significantly higher than that of normal group(P < 0.01).</p><p><b>CONCLUSIONS</b>Ct infection may cause the apoptosis of spermatogenic cells, which affords an objective evidence for illustrating the mechanism of Ct-infection-induced male infertility.</p>