Venlafaxine inhibits neuronal apoptosis in a depression rat model via ERK1/ERK2 pathway

Purpose: To investigate the effects and mechanism of action of venlafaxine on neuronal apoptosis of depressed rats. Methods: Rats were randomly divided into normal control (NC) group, depressed rats (depression) group or venlafaxine-treatment group. Changes in body weight and sucrose preference ratio were recorded and behaviors in open field test (OFT) were observed in each group. Pathological changes in and the apoptosis rate of the cerebral neurons, and the activity of extracellular signal-regulated kinase 1 (ERK1)/ERK2 pathway were observed under a microscope. Results: At weeks 2 and 4, the body weight and water consumption of rats in depression group dropped below those of rats in NC group. On the other hand, at week 2, the body weight and water consumption of rats in venlafaxine-treatment group were significantly higher than those of rats in depression group (p < 0.05). Besides, depression group had randomly arranged neuron cells and a thinner cell layer, while venlafaxine-treatment group had a relatively regular hippocampal neural cell arrangement and a thicker cell layer. Moreover, cell apoptosis rate was higher in depression group than in that NC group, and lower in venlafaxine-treatment group than that in depression group (p < 0.05). Finally, the protein expressions of phosphorylated (p)-ERK1 and p-ERK2 were significantly higher in depression group than those in NC group (p<0.05), and distinctly lower in venlafaxine-treatment group than those in depression group (p <0.05). Conclusion: By suppressing the activity of ERK1/ERK2 pathway, venlafaxine relieves the symptoms of depression and repairs neuronal injuries in rats, thereby suppressing neuronal apoptosis. Thus, these findings provide a novel approach for the development of new antidepressants

Octreotide ameliorates hypoxia/reoxygenation-induced cerebral infarction by inhibiting oxidative stress, inflammation and apoptosis, and via inhibition of TLR4/MyD88/NF-κB signaling pathway

Purpose: To explore the effects of octreotide (OCT) on oxidative stress, inflammation and apoptosis in hypoxia/reoxygenation (H/R)-induced cerebral infarction.Methods: The in vitro model of cerebral infarction was established by treating N2A cells with hypoxia for 4 h and reoxygenation for 24 h. The viability of N2A cells was determined by CCK-8 assay. The cells were divided into 3 groups: control group, H/R group, and H/R+OCT group. The cells in H/R+OCT group were pretreated with OCT (60 ng/mL) before H/R treatment. The oxidative stress of N2A cells were assessed by determining the levels of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT), reactive oxygen species (ROS) and malondialdehyde (MDA). Inflammation of N2A cells was evaluated by evaluating the levels of TNF-α, IL-1β, IL-6, and IL-8, while the apoptosis of N2A cells was assessed by flow cytometry. Western blot analysis was used to determine the expression of Bcl-2, Bax, TLR4, MyD88, and NF-κB.Results: Octreotide treatment significantly reduced the level of oxidative stress. The inflammation of N2A cells caused by hypoxia/reoxygenation was inhibited by treatment with octreotide. Apoptosis of N2A cells was also inhibited by octreotide treatment. Hypoxia/reoxygenation activated TLR4/MyD88/NF-κB signaling pathway, while octreotide inhibits the activation of this pathway.Conclusion: The results reveal that octreotide inhibits hypoxia/reoxygenation-induced oxidative stress,as well as the inflammation, and apoptosis of N2A cells by inhibiting TLR4/MyD88/NF-κB signaling pathway. Thus, these findings may provide new insights into the treatment of cerebral infarction

Benzodiazepine-Receptor Agonist Utilization in Outpatients with Anxiety Disorder: A Retrospective Study Based on Electronic Healthcare Data from a Large General Tertiary Hospital

Benzodiazepine-receptor agonists (BZRAs), including benzodiazepines (BZDs) and drugs related to BZDs (Z-drugs), are commonly used for anxiety, but often have side effects. We retrospectively investigated the utilization and prescription characteristics of BZRAs for patients with anxiety disorders in a large tertiary care general hospital between 2018 and 2021, based on electronic healthcare records. We also examined the pattern of simultaneous consumption of multiple BZRA drugs, and the diseases coexisting with anxiety that are associated with this. The numbers of patients and BZRA prescriptions increased over the 4 years. Moreover, 7195 prescriptions from 694 patients contained two or more BZRAs, of which 78.08% contained both BZDs and Z-drugs, 19.78% contained multiple BZDs, and 2.14% contained multiple Z-drugs. For anxiety patients with concomitant Alzheimer’s disease or Parkinson’s disease, and dyslipidemia, they were more likely to consume multiple BZRAs simultaneously, whereas patients with concomitant insomnia, depression, hypertension, diabetes, or tumors were less likely to consume multiple BZRAs (all p < 0.05). Furthermore, older patients who consume multiple BZRAs simultaneously may have higher probabilities of long-term drug use. Better interventions supporting standardized BZD utilization may be needed to minimize the side effects of inappropriate BZRA administration