It is well known that cobalt chloride (CoCl₂) can enhance the stability of hypoxia-inducible factor (HIF)-1α. The aim of this study is to detect the effect of CoCl₂ on the hypoxia tolerance of mice which were repeatedly exposed to autoprogressive hypoxia. Balb/c mice were randomly divided into groups of chemical pretreatment and normal saline (NS), respectively injected with CoCl₂ and NS 3 h before exposure to hypoxia for 0 run (H0), 1 run (H1), and 4 runs (H4). Western Blot, electrophoretic mobility shift assay (EMSA), extracellular recordings population spikes in area cornus ammonis I (CA 1) of mouse hippocampal slices and real-time were used in this study. Our results demonstrated that the tolerance of mice to hypoxia, the changes of HIF-1α protein level and HIF-1 DNA binding activity in mice hippocampus, the mRNA level of erythropoietin (EPO) and vascular endothelial growth factor (VEGF), and the disappearance time of population spikes of hippocampal slices were substantially different between the control group and the CoCl₂ group. Over-induction of HIF-1α by pretreatment with CoCl₂ before hypoxia did not increase the hypoxia tolerance.

Currently, the clinical management of visceral pain remains unsatisfactory for many patients suffering from this disease. While preliminary animal studies have suggested the effectiveness of gabapentin in successfully treating visceral pain, the mechanism underlying its analgesic effect remains unclear. Evidence from other studies has demonstrated the involvement of protein kinase C (PKC) and extracellular signal-regulated kinase1/2 (ERK1/2) in the pathogenesis of visceral inflammatory pain. In this study, we tested the hypothesis that gabapentin produces analgesia for visceral inflammatory pain through its inhibitory effect on the PKC-ERK1/2 signaling pathway. Intracolonic injections of formalin were performed in rats to produce colitis pain. Our results showed that visceral pain behaviors in these rats decreased after intraperitoneal injection of gabapentin. These behaviors were also reduced by intrathecal injections of the PKC inhibitor, H-7, and the ERK1/2 inhibitor, PD98059. Neuronal firing of wide dynamic range neurons in L6–S1 of the rat spinal cord dorsal horn were significantly increased after intracolonic injection of formalin. This increased firing rate was inhibited by intraperitoneal injection of gabapentin and both the individual and combined intrathecal application of H-7 and PD98059. Western blot analysis also revealed that PKC membrane translocation and ERK1/2 phosphorylation increased significantly following formalin injection, confirming the recruitment of PKC and ERK1/2 during visceral inflammatory pain. These effects were also significantly reduced by intraperitoneal injection of gabapentin. Therefore, we concluded that the analgesic effect of gabapentin on visceral inflammatory pain is mediated through suppression of PKC and ERK1/2 signaling pathways. Furthermore, we found that the PKC inhibitor, H-7, significantly diminished ERK1/2 phosphorylation levels, implicating the involvement of PKC and ERK1/2 in the same signaling pathway. Thus, our results suggest a novel mechanism of gabapentin-mediated analgesia for visceral inflammatory pain through a PKC-ERK1/2 signaling pathway that may be a future therapeutic target for the treatment of visceral inflammatory pain.

Background: Depression-related mortality and morbidity pose growing public health burdens worldwide. Although the therapeutic effect of exogenous melatonin on depression has been investigated, findings remain inconsistent. We conducted this systematic review and meta-analysis to clarify the effectiveness of melatonin in the treatment of depression, including primary and secondary depression symptoms.Methods: We searched the online databases of PubMed, EMBASE, and the Cochrane Library for original studies published up to May 2021. We used STATA 14.0 software to synthesize the results of included studies. To evaluate the effectiveness of melatonin, we calculated the standardized mean differences (SMDs) and 95% confidence intervals (CIs) of depression scores between the melatonin and placebo groups.Results: Our literature search returned 754 publications, among which 19 studies with 1,178 patients (715 women, 463 men; mean age: 56.77 years) met inclusion criteria. Melatonin dosages ranged from 2 to 25 mg per day; treatment durations were between 10 days and 3.5 years. Our synthesized results showed that melatonin was not found significantly beneficial for alleviating depressive symptoms (SMD = −0.17, 95% CI = [−0.38, 0.05]). Subgroup analysis demonstrated that the decrease in depression scores measured with the Beck Depression Inventory (BDI) was significant (SMD = −0.52, 95% CI = [−0.73, −0.31]).Conclusions: There is very limited evidence for effects of melatonin on depression.

Objective: Rapid eye movement sleep deprivation (REM-SD) can cause a decline in learning and memory and lead to changes in behavior. Therefore, REM sleep plays a key role in processes that govern learning and memory. However, the mechanism underlying REM-SD-induced learning and memory impairment is unclear and the underlying molecular signaling still needs to be identified. In the present study, we investigated the role of the cPKCγ-Ng signaling pathway in REM-SD-induced learning and memory impairment.Method: Sixty male rats were divided into Control, REM-SD, REM-SD+cPKCγ activator PMA, REM-SD+cPKCγ inhibitor H-7, and sleep revival (SR) groups. The Morris water maze was used to assess spatial learning and memory. Western blot analysis was used to detect cPKCγ total protein expression and membrane translocation levels, and Ng total protein expression and phosphorylation levels.Results: The REM-SD group performed worse on the Morris water maze test than the control group. Western blot analysis showed that cPKCγ membrane translocation and Ng phosphorylation levels were significantly lower in the REM-SD group. SR following REM-SD restored learning and memory ability, cPKCγ transmembrane translocation, and Ng phosphorylation levels, but not to levels observed before REM-SD. PMA and H-7 significantly improved/disrupted task ability as well as cPKCγ transmembrane translocation and Ng phosphorylation levels in REM-SD rats.Conclusion: The REM-SD induced learning and memory impairment in rats and may be associated with the cPKCγ-Ng signaling pathway. Specifically, activation of the cPKCγ-Ng signaling pathway may protect against REM-SD.