Peijun Ju

Bio: Peijun Ju is an academic researcher from Shanghai Jiao Tong University. The author has contributed to research in topics: Medicine & Visceral pain. The author has an hindex of 5, co-authored 15 publications receiving 96 citations.

Effects of regulating intestinal microbiota on anxiety symptoms: A systematic review

Abstract: Background Anxiety symptoms are common in mental diseases and a variety of physical disorders, especially in disorders related to stress. More and more basic studies have indicated that gut microbiota can regulate brain function through the gut-brain axis, and dysbiosis of intestinal microbiota was related to anxiety. However, there is no specific evidence to support treatment of anxiety by regulating intestinal microbiota. Aims To find evidence supporting improvement of anxiety symptoms by regulation of intestinal microbiota. Methods This systematic review of randomised controlled trials was searched based on the following databases: PubMed, EMBASE, the Cochrane Library, OVID, Web of Knowledge, China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP databases and SinoMed. The retrieval time dated back to 25 July 2018. Then we screened research literatures based on established inclusion and exclusion criteria. Quality evaluation for each included study was done using the Cochrane risk of bias and the Jadad scale. Results A total of 3334 articles were retrieved and 21 studies were included which contained 1503 subjects. In the 21 studies, 14 chose probiotics as interventions to regulate intestinal microbiota and six chose non-probiotic ways such as adjusting daily diets. Probiotic supplements in seven studies contained only one kind of probiotic, two studies used a product that contained two kinds of probiotics and the supplements used in the other five studies included at least three kinds of probiotics. In the studies that used treatment as usual plus interventions regulating intestinal flora (IRIF) as interventions (five studies), only non-probiotic ways were effective (two studies), which means 40% of studies were effective; in the studies that used IRIF alone (16 studies, 11 studies used probiotic ways and 5 studies used non-probiotic ways), 56% of studies could improve anxiety symptoms, and 80% of studies that conducted the non-probiotic interventions were effective, while 45% of studies that used probiotic supplementations had positive effects on anxiety symptoms. Overall, 11 studies showed a positive effect on anxiety symptoms by regulating intestinal microbiota, which indicated 52% of the 21 studies were effective, and there were five studies that used probiotic supplements as interventions and six used non-probiotic interventions. In addition, it should be noted that six of seven studies showed that regulation of intestinal microbiota could treat anxiety symptoms, the rate of efficacy was 86%. Conclusions We find that more than half of the studies included showed it was positive to treat anxiety symptoms by regulation of intestinal microbiota. There are two kinds of interventions (probiotic and non-probiotic interventions) to regulate intestinal microbiota, and it should be highlighted that the non-probiotic interventions were more effective than the probiotic interventions. More studies are needed to clarify this conclusion since we still cannot run meta-analysis so far.

Loss of Microglia and Impaired Brain-Neurotrophic Factor Signaling Pathway in a Comorbid Model of Chronic Pain and Depression.

Abstract: Major depressive disorder (MDD) and chronic pain are two complex disorders that often coexist. The underlying basis for this comorbidity is unknown. In the current investigation, microglia and the brain-derived neurotrophic factor (BDNF)-cAMP response element-binding protein (CREB) pathway were investigated. A comorbidity model, with characteristics of both MDD and chronic pain, was developed by the administration of dextran sodium sulfate (DSS) and the induction of chronic unpredictable psychological stress (CUS). Mechanical threshold sensory testing and the visceromotor response (VMR) were employed to measure mechanical allodynia and visceral hypersensitivity, respectively. RT-qPCR and western blotting were used to assess mRNA and protein levels of ionized calcium-binding adaptor molecule 1 (Iba-1), nuclear factor-kappa B (NF-κB), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBa), BDNF, and CREB. In comorbid animals, mechanical allodynia and visceral hypersensitivities were significant with increased mRNA and protein levels for NF-κB-p65 and IκBa. Furthermore, the comorbid animals had deceased mRNA and protein levels for Iba-1, BDNF, and CREB as well as a reduced number and density of microglia in the medial prefrontal cortex (mPFC). These results together suggest that DSS and CUS can induce the comorbidities of chronic pain and depression-like behavior. The pathology of this comorbidity involves loss of microglia within the mPFC with subsequent activation of NF-κB-p65 and down-regulation of BDNF/p-CREB signaling.

Involvement of Oxytocin Receptor/Erk/MAPK Signaling in the mPFC in Early Life Stress-Induced Autistic-Like Behaviors.

Abstract: The neonatal or infant period is a critical stage for the development of brain neuroplasticity. Early life stresses in the neonatal period, including neonatal maternal separation (NMS), have adverse effects on an increased risk of psychiatric disorders in juveniles and adults. However, the underlying molecular mechanisms are not largely understood. Here, we found that juvenile rats subjected to 4 h daily NMS during postnatal days 1 to 20 exhibited autistic-like behavioral deficits without impairments in learning and memory functions. Molecular mechanism studies showed that oxytocin receptor (OXTR) in the medial prefrontal cortex of NMS rats was evidently downregulated when compared with control pups, especially in neurons. Erk/MAPK signaling, the downstream coupling signaling of OTXR, was also inhibited in NMS juvenile rats. Treatment with oxytocin could relieve NMS-induced social deficit behaviors and activated phosphorylation of Erk/MAPK signaling. Furthermore, medication with the inhibitor of H3K4 demethylase alleviated the abnormal behaviors in NMS rats and increased the expression of OXTR in the medial prefrontal cortex, which showed an epigenetic mechanism underlying social deficits induced by NMS. Taken together, these findings identified a molecular mechanism by which disruptions of mother-infant interactions influenced later displays of typical social behaviors and suggested the potential for NMS-driven epigenetic tuning of OXTR expression.

Viral vectors as a novel tool for clinical and neuropsychiatric research applications.

Abstract: Background A viral vector is a genetically modified vector produced by genetic engineering. As pathogenic genes in the virus are completely or largely eliminated, it is safe to be widely used in multidisciplinary research fields for expressing genes, such as neuroscience, metabolism, oncology and so on. Neuroscience and psychiatry are the most closely related disciplines in either basic research or clinical research, but the application of viral vectors in neuropsychiatry has not received much attention or not been widely accepted. Objective This article will focus on the application of viral vectors in basic and clinical neuropsychiatric research. Methods By using viral vectors, scientists can perform neurological labelling, gene expression regulation and physiological manipulation for investigating phenomenon from molecular mechanisms to behaviours. At the same time, to treat mental or neurological disorders, viral vectors can be designed for gene therapy, which alter gene expression levels or repair mutated genes in the brains of patients. Perspective Viral vectors play an important role in basic research and clinical applications. To further understand brain function and prevent mental and neurological diseases, we hypothesize that viral vectors could be used along with various advanced technologies, such as sequencing and high-throughput expression analysis in the neuroscience research field.

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

Abstract: The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of coronavirus disease 2019 (COVID-19). Across the globe, a subset of patients who sustain an acute SARS-CoV-2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months. These patients are being given the diagnosis Long COVID or Post-acute sequelae of COVID-19 (PASC). It is likely that individual patients with a PASC diagnosis have different underlying biological factors driving their symptoms, none of which are mutually exclusive. This paper details mechanisms by which RNA viruses beyond just SARS-CoV-2 have be connected to long-term health consequences. It also reviews literature on acute COVID-19 and other virus-initiated chronic syndromes such as post-Ebola syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to discuss different scenarios for PASC symptom development. Potential contributors to PASC symptoms include consequences from acute SARS-CoV-2 injury to one or multiple organs, persistent reservoirs of SARS-CoV-2 in certain tissues, re-activation of neurotrophic pathogens such as herpesviruses under conditions of COVID-19 immune dysregulation, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage care for specific patients with the diagnosis.

A light- and calcium-gated transcription factor for imaging and manipulating activated neurons

Abstract: Activity remodels neurons, altering their molecular, structural, and electrical characteristics. To enable the selective characterization and manipulation of these neurons, we present FLARE, an engineered transcription factor that drives expression of fluorescent proteins, opsins, and other genetically encoded tools only in the subset of neurons that experienced activity during a user-defined time window. FLARE senses the coincidence of elevated cytosolic calcium and externally applied blue light, which together produce translocation of a membrane-anchored transcription factor to the nucleus to drive expression of any transgene. In cultured rat neurons, FLARE gives a light-to-dark signal ratio of 120 and a high- to low-calcium signal ratio of 10 after 10 min of stimulation. Opsin expression permitted functional manipulation of FLARE-marked neurons. In adult mice, FLARE also gave light- and motor-activity-dependent transcription in the cortex. Due to its modular design, minute-scale temporal resolution, and minimal dark-state leak, FLARE should be useful for the study of activity-dependent processes in neurons and other cells that signal with calcium.