Regulation of the MCHergic Neural Circuit to Dorsal Raphe Nucleus on Emotion-Related Behaviors and Intestinal Dysfunction in Mice Model of Irritable Bowel Syndrome with Diarrhea.

INTRODUCTION: Irritable bowel syndrome with diarrhea (IBS-D) is frequently accompanied by depression and anxiety, resulting in a reduced quality of life and increased medical expenditures. Although psychological factors are known to play an important role in the genesis and development of IBS-D, an understanding of the central neural control of intestinal dysfunction remains elusive. Melanin-concentrating hormone (MCH) is a gut-brain peptide involved in regulating feeding, sleep-wake rhythms, and emotional states. METHODS: This study investigated the regulation of the MCHergic neural circuit from the lateral hypothalamic area (LHA) to the dorsal raphe nucleus (DRN) on anxiety- and depression-like behaviors, intestinal motility, and visceral hypersensitivity in a mice model of IBS-D. The models of IBS-D were prepared by inducing chronic unpredictable mild stress (CUMS). RESULTS: Chemogenetic activation of the MCH neurons in the LHA could excite serotonin (5-HT) neurons in the DRN and induce anxiety- and depression-like behaviors and IBS-D-like symptoms, which could be recovered by microinjection of the MCH receptor antagonist SNAP94847 into the DRN. The mice model of IBS-D showed a reduction of 5-HT and brain-derived neurotrophic factor (BDNF) expression in the DRN, while an elevation of 5-HT and BDNF was observed in the colon through immunofluorescent staining, ELISA, and western blot analysis. SNAP94847 treatment in the DRN alleviated anxiety- and depression-like behaviors, improved intestinal motility, and alleviated visceral hypersensitivity responses by normalizing the 5-HT and BDNF expression in the DRN and colon. CONCLUSION: This study suggests that the activation of MCH neurons in the LHA may induce IBS-D symptoms via the DRN and that the MCH receptor antagonist could potentially have therapeutic effects.

The role of ncRNAs in depression.

Depressive disorders have a significant impact on public health, and depression have an unsatisfactory recurrence rate and are challenging to treat. Non-coding RNAs (ncRNAs) are RNAs that do not code protein, which have been shown to be crucial for transcriptional regulation. NcRNAs are important to the onset, progress and treatment of depression because they regulate various physiological functions. This makes them distinctively useful as biomarkers for diagnosing and tracking responses to therapy among individuals with depression. It is important to seek out and summarize the research findings on the impact of ncRNAs on depression since significant advancements have been made in this area recently. Hence, we methodically outlined the findings of published researches on ncRNAs and depression, focusing on microRNAs. Above all, this review aims to improve our understanding of ncRNAs and provide new insights of the diagnosis and treatment of depression.

The effect of butylphthalide on improving the neurological function of patients with acute anterior circulation cerebral infarction after mechanical thrombectomy.

Butylphthalide can improve blood circulation in patients with acute cerebral infarction. Complement 3a receptor 1 (C3aR1) is involved in the regulation of innate immune response and pathogen monitoring, which is closely related to the pathophysiological processes of breast cancer, neurogenesis and lipid catabolism. Our study explored the therapeutic effect of butylphthalide on improving the neurological function of patients with acute anterior circulation cerebral infarction after mechanical thrombectomy, and evaluated the correlation between serum C3aR1 and butylphthalide on improving the neurological function after mechanical thrombectomy. 288 patients with acute anterior circulation cerebral infarction who were admitted to our hospital from January 2019 to November 2022 and were treated with mechanical thrombectomy for the first time were included in this retrospective study and divided into the butylphthalide group and control group that they received treatment methods. The National Institutes of Health Stroke Scale (NIHSS) scale was used to evaluate the patient neurological function treatment efficacy, and the modified Rankin Scale (mRS) scale was used to measure the patient neurological function status 3 months after surgery. Enzyme-linked immunosorbent assay method was used to determine the content of C3aR1 in serum. Two weeks after thrombus removal, the NIHSS efficacy of the butylphthalide group and the control group were 94.44% and 72.22%, respectively. The butylphthalide group was significantly higher than the control group (P < .001). Three months after the operation, the mRS score of the butylphthalide group was significantly lower than that of the control group (P = .001), and the excellent and good rate was significantly higher than that of the control group (P < .001). The serum C3aR1 level of the butylphthalide group was significantly lower than that of the control group 2 weeks after operation and 3 months after operation (P < .001). The serum C3aR1 was positively correlated with the efficacy of NIHSS (R = 0.815, P = .004), which was positively correlated with mRS score (R = 0.774, P = .007). Butylphthalide can improve the therapeutic effect of neurological function in patients with acute anterior circulation cerebral infarction after mechanical thrombus removal. The patient serum C3aR1 is related to the patient neurotherapy efficacy and neurological function status, and its level can reflect the patient neurological function recovery to a certain extent.