Dysfunction of the noradrenergic (NE) neurons is implicated in the pathogenesis of bipolar disorder (BPD). ErbB4 is highly expressed in NE neurons, and its genetic variation has been linked to BPD; however, how ErbB4 regulates NE neuronal function and contributes to BPD pathogenesis is unclear. Here we find that conditional deletion of ErbB4 in locus coeruleus (LC) NE neurons increases neuronal spontaneous firing through NMDA receptor hyperfunction, and elevates catecholamines in the cerebrospinal fluid (CSF). Furthermore, Erbb4-deficient mice present mania-like behaviors, including hyperactivity, reduced anxiety and depression, and increased sucrose preference. These behaviors are completely rescued by the anti-manic drug lithium or antagonists of catecholaminergic receptors. Our study demonstrates the critical role of ErbB4 signaling in regulating LC-NE neuronal function, reinforcing the view that dysfunction of the NE system may contribute to the pathogenesis of mania-associated disorder.

Acne vulgaris is one of the most common chronic inflammatory skin diseases. Bergamot and sweet orange are rich in nutritional and functional components, which exhibit antioxidant, anti-inflammatory, and antiapoptotic effect. The aim of this study was to evaluate the potential effect of bergamot and sweet orange (juice and essential oil) on acne vulgaris caused by excessive secretion of androgen. Eighty male golden hamsters were randomly divided into 10 groups and received low or high dose of bergamot and sweet orange juice and essential oil, physiological saline, and positive drugs for four weeks, respectively. Results showed that all interventions could improve acne vulgaris by reducing the growth rate of sebaceous gland spots, inhibiting TG accumulation, decreasing the release of inflammatory cytokines (notably reducing IL-1α levels), promoting apoptosis in the sebaceous gland, and decreasing the ratio of T/E₂. Among them, bergamot and orange essential oil may have better effects (dose dependent) on alleviating acne vulgaris than the corresponding juice. In view of the large population of acne patients and the widespread use of sweet orange and bergamot, this study is likely to exert an extensive and far-reaching influence.

A large body of data has confirmed that α7 nicotinic acetylcholine receptors (nAChRs) play a pivotal role in cognition, memory, and other neuropsychiatric diseases, but their effect on seizure susceptibility in C57BL/6 wild-type mice is not fully understood. Here, we showed that decreased activity of α7 nAChRs could increase the excitability of CA1 pyramidal neurons and shorten the onset time of epilepsy in pilocarpine-induced mouse models. However, compared with the control group, there was no apparent effect of increasing the activity of α7 nAChRs. Moreover, the expression of α7 nAChRs is downregulated in human epileptogenic tissues. Taken together, our findings indicate that α7 nAChR is an essential regulator of seizure susceptibility.

The aim of this study was to investigate the effect of the P2Y2 receptor (P2Y2R) signaling pathway on neuronal regeneration and angiogenesis during spinal cord injury (SCI). The rats were randomly divided into 3 groups, including the sham+dimethyl sulfoxide (DMSO), SCI+DMSO, and SCI+P2Y2R groups. The SCI animal models were constructed. A locomotor rating scale was used for behavioral assessments. The apoptosis of spinal cord tissues was detected by TUNEL staining. The expression levels of P2Y2R, GFAP, nestin, Tuj1, and CD34 were detected by immunofluorescence staining, and the expression levels of TNF-α, IL-1β, and IL-6 were detected by enzyme-linked immunosorbent assay. The locomotor score in the model group was significantly lower than the sham group. The expression of P2Y2R was increased after SCI. The expression levels of TNF-α, IL-1β, and IL-6 were increased remarkably in the SCI model group compared with the sham group. The P2Y2R inhibitor relieved neuronal inflammation after SCI. Compared with the sham group, the apoptotic rate of spinal cord tissue cells in the model group was significantly increased. The P2Y2R inhibitor reduced the apoptosis of the spinal cord tissue. The expressions of CD34, Tuj1, and nestin in the model group were decreased, while the expressions of GFAP and P2Y2R were increased. The P2Y2R inhibitor reversed their expression levels. The P2Y2R inhibitor could alleviate SCI by relieving the neuronal inflammation, inhibiting the spinal cord tissue apoptosis, and promoting neuronal differentiation and vascular proliferation after SCI. P2Y2R may serve as a target for the treatment of SCI.

Background: Sleep disorders significantly affect the quality of life in Parkinson disease (PD) patients. Deep brain stimulation of the subthalamic nucleus has been reported to improve motor symptoms and decrease medication usage. However, the impact of subthalamic nucleus deep brain stimulation (STN-DBS) on sleep quality in PD patients remains to be definitively determined. This systematic review and meta-analysis, conducted following the preferred reporting items for systematic reviews and meta-analyses guidelines, aimed to clarify the effect of STN-DBS on sleep quality in PD patients. Methods: A rigorous literature search identified 6 studies, including 1 randomized controlled trial and 5 self-controlled trials, totaling 154 patients who underwent deep brain stimulation, providing 308 pairs of data for analysis. Parkinson disease sleep scale was the primary measure of interest, while the Movement Disorder Society-sponsored revision of the unified Parkinson disease rating scale was documented in all trials. Study quality was assessed using the Newcastle-Ottawa scale. Results: STN-DBS significantly improved Parkinson disease sleep scale scores (mean difference = 20.41, 95% CI: [13.03, 27.79], I² = 60.8%, P < .001), indicating enhanced sleep quality. Furthermore, a significant reduction in movement disorder society unified Parkinson disease rating scale part III scores postoperatively (mean difference = −12.59, 95% CI: [−14.70, −10.49], I² = 89.9%, P < .001) suggested improved motor function. PD medication usage was also significantly reduced postoperatively (mean difference = −314.71, 95% CI: [−468.13, −161.28], I² = 52.9%, P < .001). A sensitivity analysis confirmed the robustness of the main findings. The sample size was adequate, allowing for conclusive inferences. Conclusion: The present study, which comprises a comprehensive systematic review and meta-analysis, offers compelling evidence that STN-DBS can ameliorate sleep quality, augment motor function, and curtail medication consumption among individuals afflicted with PD.

Objective: The association of fat mass and obesity-related (FTO) gene with osteoarthritis (OA) risk has been investigated in multiple genome-wide association studies but showed inconsistent results. Our study aimed to assess FTO expression in different OA sequencing datasets and to meta-analyze whether FTO polymorphism was associated with the risk of osteoarthritis.Method: Gene expression profiles were obtained from ArrayExpress, Gene Expression Omnibus (GEO), and BioProject databases. Three electronic databases including PubMed and EMBASE were systematically retrieved to identify articles exploring the association between FTO polymorphisms and OA risk published before September 2022. Summary odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to perform the result. Stata software was utilized to conduct analyses on predetermined ethnicity and gender subgroups and sensitivity.Results: FTO gene was differentially expressed in the datasets from the UK. This systematic review and meta-analysis encompasses eight studies that revealed a significant association between FTO polymorphisms and OA risk [OR 1.07, 95% CI (1.03, 1.11), P < 0.001] in the overall population. In subgroup analysis, a marked association was observed in European Caucasian [OR 1.08, 95% CI (1.04–1.12), P < 0.001] and North American Caucasian with the Asian subgroups [OR 0.98, 95% CI (0.83–1. 6), P = 0.83] as an exception. Among the studies, four of them demonstrated attenuation in their OA risk after body mass index (BMI) adjustment in Caucasian populations.Conclusion: FTO significant differential expression was associated with the increased risk of OA in Caucasian populations. Nevertheless, the causality between FTO polymorphisms and OA risk remains largely elusive. Hence, further studies with larger sample size are necessary to validate whether FTO gene polymorphism contributes to OA susceptibility.