Effects of exercise interventions on brain-derived neurotrophic factor levels in overweight and obesity: A systematic review and meta-analysis.

Background: /Objective. An explosion in global obesity epidemic poses threats to the healthcare system by provoking risks of many debilitating diseases, including cognitive dysfunction. Physical activity has been shown to alleviate the deleterious effects of obesity-associated cognitive deficits across the lifespan. Given the strong neuroprotective role of brain-derived neurotrophic factor (BDNF) and exercise training as a known modulator for its elevation, this systematic review sought to examine the strength of the association between exercise and BDNF levels in healthy people with overweight and obesity. Methods: Six electronic databases (PubMed, MEDLINE, EMBASE, Web of Science, Ovid Nursing Database, and SPORTDiscus) were searched from their inceptions through December 2022. The primary outcome of interest was BDNF levels. Interventional studies (randomized and quasi-experimental) with English full text available were included. Risk of bias of the included studies was assessed using the Physiotherapy Evidence Database Scale. Data were extracted for meta-analyses by random-effects models. Results: Thirteen studies (n = 750), of which 69.2% (9/13) had low risk of bias, were included. In the meta-analysis, exercise interventions had no significant effect on resting BDNF levels (standardized mean difference: -0.30, 95% CI -0.80 to 0.21, P = 0.25). Subgroup analyses also indicated no effects of age and types of control groups being compared on moderating the association. Conclusion: To further inform the role of BDNF in obesity-related cognitive functioning, rigorous studies with larger samples of participants and raw data available were imperatively deserved.

Sex differences in brain excitability revealed by concurrent iTBS/fNIRS.

Sex differences have been claimed an imperative factor in the optimization of psychiatric treatments. Intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation, is a promising non-invasive treatment option. Here, we investigated whether the real-time neural response to iTBS differs between men and women, and which mechanisms may mediate these differences. To this end, we capitalized on a concurrent iTBS/functional near-infrared spectroscopy setup over the left dorsolateral prefrontal cortex, a common clinical target, to test our assumptions. In a series of experiments, we show (1) a biological sex difference in absolute hemoglobin concentrations in the left dorsolateral prefrontal cortex in healthy participants; (2) that this sex difference is amplified by iTBS but not by cognitive tasks; and (3) that the sex difference amplified by iTBS is modulated by stimulation intensity. These results inform future stimulation treatment optimizations towards precision psychiatry.

Effect of exercise interventions on brain-derived neurotrophic factor expression in people with overweight and obesity: protocol for a systematic review and meta-analysis.

INTRODUCTION: Epidemic obesity ('globobesity') has led to a considerable rise in the prevalence and incidence of many disabling conditions, including cognitive dysfunction. Recent evidence has suggested that habitual exercise can alleviate the deleterious effects of obesity on cognitive functioning across the lifespan. Given that there is a potential link among obesity, exercise, cognitive health and brain-derived neurotrophic factor (BDNF), this systematic review aims to critically appraise interventional trials on exercise and BDNF and to estimate the pooled effect of exercise training on BDNF levels among healthy individuals with overweight and obesity. METHODS AND ANALYSIS: Six electronic databases-PubMed, MEDLINE, EMBASE, Web of Science, Ovid Nursing Database and SPORTDiscus-will be searched from their inception through December 2022. Only interventional studies, including randomised controlled trials and quasi-experimental studies, with full text available and reported in English will be included. The primary outcomes will be changes in BDNF levels among healthy subjects with overweight and obesity following either acute or chronic bouts of exercise interventions. Two reviewers will independently conduct data extraction and risk of bias assessment for included trials using the Physiotherapy Evidence Database Scale. We will produce a narrative synthesis, with findings categorised by sex, age groups and types of exercise training. Data will be extracted and pooled for meta-analyses using random-effects models. ETHICS AND DISSEMINATION: No formal ethical approval is required for this systematic review. The findings of this review will be disseminated through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42023414868.

Effects of Voluntary Wheel Running Exercise on Chemotherapy-Impaired Cognitive and Motor Performance in Mice.

Chemotherapy-induced cognitive impairment (chemobrain) and muscle wasting (cachexia) are persisting side effects which adversely affect the quality of life of cancer survivors. We therefore investigated the efficacy of physical exercise as a non-pharmacological intervention to reverse the adverse effects of chemotherapy. We examined whether physical exercise in terms of voluntary wheel running could prevent chemotherapy-induced cognitive and motor impairments in mice treated with the multi-kinase inhibitor sorafenib. Adult male BALB/c mice were subdivided into runner and non-runner groups and orally administered with sorafenib (60 mg/kg) or vehicle continuously for four weeks. Mice could freely access the running wheel anytime during sorafenib or vehicle treatment. We found that sorafenib treatment reduced body weight gain (% of change, vehicle: 3.28 ± 3.29, sorafenib: -9.24 ± 1.52, p = 0.0004), impaired hippocampal-dependent spatial memory in the Y maze (exploration index, vehicle: 35.57 ± 11.38%, sorafenib: -29.62 ± 7.90%, p < 0.0001), increased anhedonia-like behaviour in the sucrose preference test (sucrose preference, vehicle: 66.57 ± 3.52%, sorafenib: 44.54 ± 4.25%, p = 0.0005) and impaired motor skill acquisition in rotarod test (latency to fall on day 1: 37.87 ± 8.05 and day 2: 37.22 ± 12.26 s, p > 0.05) but did not induce muscle wasting or reduce grip strength. Concomitant voluntary running reduced anhedonia-like behaviour (sucrose preference, sedentary: 44.54 ± 4.25%, runners: 59.33 ± 4.02%, p = 0.0357), restored impairment in motor skill acquisition (latency to fall on day 1: 50.85 ± 15.45 and day 2: 168.50 ± 37.08 s, p = 0.0004), but failed to rescue spatial memory deficit. Immunostaining results revealed that sorafenib treatment did not affect the number of proliferating cells and immature neurons in the hippocampal dentate gyrus (DG), whereas running significantly increased cell proliferation in both vehicle- (total Ki-67+ cells, sedentary: 16,687.34 ± 72.63, exercise: 3320.03 ± 182.57, p < 0.0001) and sorafenib-treated mice (Ki-67+ cells in the ventral DG, sedentary: 688.82.34 ± 38.16, exercise: 979.53 ± 73.88, p < 0.0400). Our results suggest that spatial memory impairment and anhedonia-like behaviour precede the presence of muscle wasting, and these behavioural deficits are independent of the changes in adult hippocampal neurogenesis. Running effectively prevents body weight loss, improves motor skill acquisition and reduces anhedonia-like behaviour associated with increased proliferating cells and immature neurons in DG. Taken together, they support physical exercise rehabilitation as an effective strategy to prevent chemotherapy side effects in terms of mood dysregulation and motor deficit.

Leveraging the glymphatic and meningeal lymphatic systems as therapeutic strategies in Alzheimer's disease: an updated overview of nonpharmacological therapies.

Understanding and treating Alzheimer's disease (AD) has been a remarkable challenge for both scientists and physicians. Although the amyloid-beta and tau protein hypothesis have largely explained the key pathological features of the disease, the mechanisms by which such proteins accumulate and lead to disease progression are still unknown. Such lack of understanding disrupts the development of disease-modifying interventions, leaving a therapeutic gap that remains unsolved. Nonetheless, the recent discoveries of the glymphatic pathway and the meningeal lymphatic system as key components driving central solute clearance revealed another mechanism underlying AD pathogenesis. In this regard, this narrative review integrates the glymphatic and meningeal lymphatic systems as essential components involved in AD pathogenesis. Moreover, it discusses the emerging evidence suggesting that nutritional supplementation, non-invasive brain stimulation, and traditional Chinese medicine can improve the pathophysiology of the disease by increasing glymphatic and/or meningeal lymphatic function. Given that physical exercise is a well-regarded preventive and pro-cognitive intervention for dementia, we summarize the evidence suggesting the glymphatic system as a mediating mechanism of the physical exercise therapeutic effects in AD. Targeting these central solute clearance systems holds the promise of more effective treatment strategies.

Increasing Adiponectin Signaling by Sub-Chronic AdipoRon Treatment Elicits Antidepressant- and Anxiolytic-Like Effects Independent of Changes in Hippocampal Plasticity.

(1) Background: Adiponectin is an adipocyte-secreted hormone that has antidepressant- and anxiolytic-like effects in preclinical studies. Here, we investigated the antidepressant- and anxiolytic-like effects of sub-chronic treatment with AdipoRon, an adiponectin receptor agonist, and its potential linkage to changes in hippocampal adult neurogenesis and synaptic plasticity. (2) Methods: Different cohorts of wild-type C57BL/6J and CamKIIα-Cre male mice were treated with sub-chronic (7 days) AdipoRon, followed by behavioral, molecular, and electrophysiological experiments. (3) Results: 7-day AdipoRon treatment elicited antidepressant- and anxiolytic-like effects but did not affect hippocampal neurogenesis. AdipoRon treatment reduced hippocampal brain-derived neurotrophic factor (BDNF) levels, neuronal activation in the ventral dentate gyrus, and long-term potentiation of the perforant path. The knockdown of N-methyl-D-aspartate (NMDA) receptor subunits GluN2A and GluN2B in the ventral hippocampus did not affect the antidepressant- and anxiolytic-like effects of AdipoRon. (4) Conclusions: Increasing adiponectin signaling through sub-chronic AdipoRon treatment results in antidepressant- and anxiolytic-like effects independent of changes in hippocampal structural and synaptic function.

Multi-systemic evaluation of biological and emotional responses to the Trier Social Stress Test: A meta-analysis and systematic review.

Humans experience multiple biological and emotional changes under acute stress. Adopting a multi-systemic approach, we summarized 61 studies on healthy people's endocrinological, physiological, immunological and emotional responses to the Trier Social Stress Test. We found salivary cortisol and negative mood states were the most sensitive markers to acute stress and recovery. Biomarkers such as heart rate and salivary alpha-amylase also showed sensitivity to acute stress, but the numbers of studies were small. Other endocrinological (e.g., dehydroepiandrosterone), inflammatory (C-Reactive Protein, Interleukin-6) and physiological (e.g., skin conductance level) measures received modest support as acute stress markers. Salivary cortisol showed some associations with mood measures (e.g., state anxiety) during acute stress and recovery, and heart rate showed preliminary positive relationship with calmness ratings during response to TSST, but the overall evidence was mixed. While further research is needed, these findings provide updated and comprehensive knowledge on the integrated psychobiological response profiles to TSST.

Exercise effect on the gut microbiota in young adolescents with subthreshold depression: A randomized psychoeducation-controlled Trial.

This 3-month randomized psychoeducation-controlled trial (RCT) of exercise was undertaken in young adolescents with subthreshold depression to examine the impact on gut microbiota. Participants (aged 12-14 years) were randomly assigned to an exercise or a psychoeducation-controlled group. The exercise intervention arm took moderate-intensity exercise, comprised of 30 min of running per day, 4 days a week for 3 months. Psychoeducation intervention consisted of 6 sessions of group activity including gaming, reading, and singing. The gut microbiota was assessed by metagenomic sequencing. After 3-month moderate-intensity exercise, the intervention group increased the relative abundance of Coprococcus, Blautia, Dorea, Tyzzerella at the genus level, as well as Tyzzerella nexilis, Ruminococcus obeum at species level when compared to the psychoeducation-controlled group. Moreover, EggNOG analyses showed that the defense and signal transduction mechanism were highly enriched after the active intervention, and changes were correlated with improvements in depressive symptoms measured by Chinese Patient Depression Questionnaire 9. The KEGG pathway of neurodegenerative diseases was depleted in the microbiome in young adolescents with subthreshold depression after exercise intervention. This 3-month RCT suggests that at both the genus and species levels, aerobic group exercise intervention improved in depressive symptoms and revealed changes in gut microbiota suggesting beneficial effects.

Central Adiponectin Signaling - A Metabolic Regulator in Support of Brain Plasticity.

Brain plasticity and metabolism are tightly connected by a constant influx of peripheral glucose to the central nervous system in order to meet the high metabolic demands imposed by neuronal activity. Metabolic disturbances highly affect neuronal plasticity, which underlies the prevalent comorbidity between metabolic disorders, cognitive impairment, and mood dysfunction. Effective pro-cognitive and neuropsychiatric interventions, therefore, should consider the metabolic aspect of brain plasticity to achieve high effectiveness. The adipocyte-secreted hormone, adiponectin, is a metabolic regulator that crosses the blood-brain barrier and modulates neuronal activity in several brain regions, where it exerts neurotrophic and neuroprotective properties. Moreover, adiponectin has been shown to improve neuronal metabolism in different animal models, including obesity, diabetes, and Alzheimer's disease. Here, we aim at linking the adiponectin's neurotrophic and neuroprotective properties with its main role as a metabolic regulator and to summarize the possible mechanisms of action on improving brain plasticity via its role in regulating the intracellular energetic activity. Such properties suggest adiponectin signaling as a potential target to counteract the central metabolic disturbances and impaired neuronal plasticity underlying many neuropsychiatric disorders.

Global hippocampus functional connectivity as a predictive neural marker for conversion to future mood disorder in unaffected offspring of bipolar disorder parents.

OBJECTIVES: Hippocampus-related functional alteration in genetically at-risk individuals may reflect an endophenotype of a mood disorder. Herein, we performed a prospective study to investigate whether baseline hippocampus functional connectivity (FC) in offspring of patients with bipolar disorder (BD) would predict subsequent conversion to mood disorder. METHODS: Eighty bipolar offspring and 40 matched normal controls (NC) underwent resting state functional MRI (rsfMRI) scanning on a 3.0 Tesla MR scanner. The offspring were subdivided into asymptomatic offspring (AO) (n = 41) and symptomatic offspring (SO) (n = 39) according to whether they manifested subthreshold mood symptoms. After identifying the different hippocampus FCs between the AO and SO, a logistic regression analysis was conducted to investigate whether the baseline hippocampus FCs predicted a future mood disorder during a 6-year follow-up. RESULTS: We identified seven baseline para/hippocampus FCs that showed differences between AO and SO, which were entered as predictive features in the logistic regressive model. Of the 80 bipolar offspring entering the analysis, the FCs between left hippocampus and left precuneus, and between right hippocampus and left posterior cingulate, showed a discriminative capacity for predicting future mood disorder (area-under-curve, or AUC=75.76 % and 75.00 % respectively), and for predicting BD onset (AUC=77.46 % and 81.63 %, respectively). CONCLUSIONS: The present findings revealed high predictive utility of the hippocampus resting state FCs for future mood disorder and BD onset in individuals at familial risk. These neural markers can potentially improve early detection of individuals carrying particularly high risk for future mood disorder.

Potential mechanisms underlying the accelerated cognitive decline in people with chronic low back pain: A scoping review.

A growing body of evidence has shown that people with chronic low back pain (CLBP) demonstrate significantly greater declines in multiple cognitive domains than people who do not have CLBP. Given the high prevalence of CLBP in the ever-growing aging population that may be more vulnerable to cognitive decline, it is important to understand the mechanisms underlying the accelerated cognitive decline observed in this population, so that proper preventive or treatment approaches can be developed and implemented. The current scoping review summarizes what is known regarding the potential mechanisms underlying suboptimal cognitive performance and cognitive decline in people with CLBP and discusses future research directions. Five potential mechanisms were identified based on the findings from 34 included studies: (1) altered activity in the cortex and neural networks; (2) grey matter atrophy; (3) microglial activation and neuroinflammation; (4) comorbidities associated with CLBP; and (5) gut microbiota dysbiosis. Future studies should deepen the understanding of mechanisms underlying this association so that proper prevention and treatment strategies can be developed.

Non-Invasive Brain Stimulation Effects on Biomarkers of Tryptophan Metabolism: A Scoping Review and Meta-Analysis.

Abnormal activation of the kynurenine and serotonin pathways of tryptophan metabolism is linked to a host of neuropsychiatric disorders. Concurrently, noninvasive brain stimulation (NIBS) techniques demonstrate high therapeutic efficacy across neuropsychiatric disorders, with indications for modulated neuroplasticity underlying such effects. We therefore conducted a scoping review with meta-analysis of eligible studies, conforming with the PRISMA statement, by searching the PubMed and Web of Science databases for clinical and preclinical studies that report the effects of NIBS on biomarkers of tryptophan metabolism. NIBS techniques reviewed were electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS). Of the 564 search results, 65 studies were included with publications dating back to 1971 until 2022. The Robust Bayesian Meta-Analysis on clinical studies and qualitative analysis identified general null effects by NIBS on biomarkers of tryptophan metabolism, but moderate evidence for TMS effects on elevating serum serotonin levels. We cannot interpret this as evidence for or against the effects of NIBS on these biomarkers, as there exists several confounding methodological differences in this literature. Future controlled studies are needed to elucidate the effects of NIBS on biomarkers of tryptophan metabolism, an under-investigated question with substantial implications to clinical research and practice.

Differential Relationships Among C-Reactive Protein, Attention Functioning, and Brain Structure in Bipolar Offspring With and Without Subthreshold Mood Symptoms.

Background: Bipolar disorder (BD) is a highly heritable mood disorder. Activated low-grade inflammation may not only play an adverse role in the pathophysiology of BD, but also contribute to a resilience process. The neuroinflammatory processes may underlie the attention deficit and alteration of gray matter volume (GMV) in the early stage and premorbid period of BD. Also, the differential inflammation-brain relationship may be identified as biological markers for BD pathology or resilience.Methods: The present data were collected between March 2013 and June 2016. Sixty-four offspring of BD patients were recruited and subdivided into asymptomatic (n = 33, mean age = 17.8 years) and symptomatic (n = 31, mean age = 16.2 years) groups according to whether they manifested subthreshold mood symptoms. The diagnosis of BD was confirmed according to DSM-IV criteria. C-reactive protein (CRP) level, attention functioning, and GMV data were measured by ELISA, the Continuous Performance Test-Identical Pair test (CPT-IP), and 3.0 T magnetic resonance imaging, respectively. Their relationships were examined with mediation and moderation analyses.Results: We observed a higher level of CRP and poorer attention in the symptomatic group than the asymptomatic group and found a significant group × CRP interactive effect on GMV in regions spanning right precentral and postcentral gyri (P = .043). CRP levels negatively mediated the relationship between the group and CPT-IP scores, and the group marginally moderated the relationship between pre/postcentral gyri volumes and CPT-IP scores (P = .05).Conclusions: Symptomatic and asymptomatic bipolar offspring manifested differential inflammation-GMV-attention relationships, which may represent, respectively, an endophenotype or a resilience process for BD.

Comparative effectiveness of exercise, antidepressants and their combination in treating non-severe depression: a systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVE: To assess the comparative effectiveness of exercise, antidepressants and their combination for alleviating depressive symptoms in adults with non-severe depression. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Embase, MEDLINE, PsycINFO, Cochrane Library, Web of Science, Scopus and SportDiscus. ELIGIBILITY CRITERIA: Randomised controlled trials (1990-present) that examined the effectiveness of an exercise, antidepressant or combination intervention against either treatment alone or a control/placebo condition in adults with non-severe depression. STUDY SELECTION AND ANALYSIS: Risk of bias, indirectness and the overall confidence in the network were assessed by two independent investigators. A frequentist network meta-analysis was performed to examine postintervention differences in depressive symptom severity between groups. Intervention drop-out was assessed as a measure of treatment acceptability. RESULTS: Twenty-one randomised controlled trials (n=2551) with 25 comparisons were included in the network. There were no differences in treatment effectiveness among the three main interventions (exercise vs antidepressants: standardised mean differences, SMD, -0.12; 95% CI -0.33 to 0.10, combination versus exercise: SMD, 0.00; 95% CI -0.33 to 0.33, combination vs antidepressants: SMD, -0.12; 95% CI -0.40 to 0.16), although all treatments were more beneficial than controls. Exercise interventions had higher drop-out rates than antidepressant interventions (risk ratio 1.31; 95% CI 1.09 to 1.57). Heterogeneity in the network was moderate (τ2=0.03; I2=46%). CONCLUSIONS: The results suggest no difference between exercise and pharmacological interventions in reducing depressive symptoms in adults with non-severe depression. These findings support the adoption of exercise as an alternative or adjuvant treatment for non-severe depression in adults. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD4202122656.

Altered Cytokine and BDNF Levels in Individuals with Autism Spectrum Disorders.

Previous studies have shown that immunological factors are involved in the pathogenesis of autism spectrum disorders (ASDs). The present study examined whether immunological abnormalities are associated with cognitive and behavioral deficits in children with ASD and whether children with ASD show different immunological biomarkers and brain-derived neurotrophic factor BDNF levels than typically developing (TD) children. Sixteen children with TD and 18 children with ASD, aged 6-18 years, voluntarily participated in the study. Participants' executive functions were measured using neuropsychological tests, and behavioral measures were measured using parent ratings. Immunological measures were assessed by measuring the participants' blood serum levels of chemokine ligand 2 (CCL2) and chemokine ligand 5 (CCL5). Children with ASD showed greater deficits in cognitive functions as well as altered levels of immunological measures when compared to TD children, and their cognitive functions and behavioral deficits were significantly associated with increased CCL5 levels and decreased BDNF levels. These results provide evidence to support the notion that altered immune functions and neurotrophin deficiency are involved in the pathogenesis of ASD.

Restorative Action of Vitamin D3 on Motor Dysfunction Through Enhancement of Neurotrophins and Antioxidant Expression in the Striatum.

A number of studies has explored a positive correlation between low levels of serum Vitamin D3 (VD; cholecalciferol) and development of neurodegenerative diseases including Huntington's disease (HD). In the present study, the prophylactic effect of VD on motor dysfunction was studied in an experimental model of HD. An HD-like syndrome was induced in male C57BL/6 mice through an intraperitoneal injection (i.p) of 3-NP for 3 consecutive doses at 12 h interval of time as described previously (Amende et al. 2005). This study investigated thein-vivotherapeutic potential of VD (500 IU/kg/day) supplementation on movement, motor coordination, motor activity and biochemical changes in this HD model. Mice were divided into four groups: Group I: Control (saline); Group II: 3-NP induced HD (HD); Group III: Vitamin D3 (VD) and Group IV: 3-NP induced + post Vitamin D3 injection (HD + VD). All groups of mice were tested for locomotion, gait analysis and rotarod performances over a span of 30-days. VD administration rescued locomotor dysfunction and neuromuscular impairment in HD mice with no change in gait dynamics. In addition, administration of VD to 3-NP treated mice led to a significant enhancement in the expression of key neurotrophic factors including brain-derived neurotrophic factor (BDNF) and nerve-growth factor (NGF), the Vitamin D receptor (VDR), and antioxidant markers (catalases [Cat] and glutathione peroxidase [GpX4]) in the striatum, suggesting a detoxification effect of VD. Altogether, our results show that VD supplementation induces survival signals, diminishes oxidative stress, and reduces movement and motor dysfunction in HD.

Synergistic effects of two naturally occurring iridoids in eliciting a rapid antidepressant action by up-regulating hippocampal PACAP signalling.

BACKGROUND AND PURPOSE: Current mainstream antidepressants have limited efficacy with a delayed onset of action. Yueju, a herbal medicine, has a rapid antidepressant action. Identification of the active ingredients in Yueju and the mechanism/s involved was carried out. EXPERIMENTAL APPROACH: Key molecule/s and compounds involved in this antidepressant action was identified by transcriptomic and HPLC analysis, respectively. Antidepressant effects were evaluated using various behavioural experiments. The signalling involved was assessed using site-directed pharmacological intervention or optogenetic manipulation. KEY RESULTS: Transcriptomic analysis showed that Yueju up-regulated pituitary adenylate cyclase activating polypeptide (PACAP) expression in the hippocampus. Two iridoids, geniposide and shanzhiside methyl ester, were identified and quantified from Yueju. Only co-treatment with both, at an equivalent concentrations found in Yueju, increased PACAP expression and elicited a rapid antidepressant action, which were blocked by intra-dentate gyrus infusion of a PACAP antagonist or optogenetic inactivation of PACAP expressing neurons. Geniposide and shanzhiside methyl ester co-treatment rapidly inhibited CaMKII phosphorylation and enhanced mTOR/4EBP1/P70S6k/BDNF ignalling, while intra-dentate gyrus infusions of a CaMKII activator blunted the rapid antidepressant action and BDNF expression up-regulation induced by the co-treatment. A single co-treatment of them rapidly improved depression-like behaviours and up-regulated hippocampal PACAP signalling in the repeated corticosterone-induced depression model, further confirming the involvement of PACAP. CONCLUSION AND IMPLICATIONS: Geniposide and shanzhiside methyl ester co-treatment had a synergistic rapid onset antidepressant action by triggering hippocampal PACAP activity and associated CaMKII-BDNF signalling. This mechanism could be targeted for development of fast onset antidepressants.

The Role of MicroRNA and Microbiota in Depression and Anxiety.

Depression and anxiety are devastating disorders. Understanding the mechanisms that underlie the development of depression and anxiety can provide new hints on novel treatments and preventive strategies. Here, we summarize the latest findings reporting the novel roles of gut microbiota and microRNAs (miRNAs) in the pathophysiology of depression and anxiety. The crosstalk between gut microbiota and the brain has been reported to contribute to these pathologies. It is currently known that some miRNAs can regulate bacterial growth and gene transcription while also modulate the gut microbiota composition, suggesting the importance of miRNAs in gut and brain health. Treatment and prevention strategies for neuropsychiatric diseases, such as physical exercise, diet, and probiotics, can modulate the gut microbiota composition and miRNAs expressions. Nonetheless, there are critical questions to be addressed to understand further the mechanisms involved in the interaction between the gut microbiota and miRNAs in the brain. This review summarizes the recent findings of the potential roles of microbiota and miRNA on the neuropathology of depression and anxiety, and its potential as treatment strategies.

Dose-response relationship between iTBS and prefrontal activation during executive functioning: A fNIRS study.

Introduction: Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation paradigm that has demonstrated promising therapeutic benefits for a variety of neuropsychiatric disorders. It has recently garnered widespread favor among researchers and clinicians, owing to its comparable potentiation effects as conventional high-frequency repetitive transcranial magnetic stimulation (rTMS), but administered in a much shorter time frame. However, there is still a lack of agreement over the optimal stimulation intensity, particularly when targeting the prefrontal regions. The objective of this study was to systematically investigate the influence of different stimulation intensities of iTBS, applied over the left dorsolateral prefrontal cortex (DLPFC), on brain activity and executive function in healthy adults. Methods: Twenty young healthy adults were enrolled in this randomized cross-over experiment. All participants received a single session iTBS over the left DLPFC at intensities of 50, 70, or 100% of their individual resting motor threshold (RMT), each on separate visits. Functional near-infrared spectroscopy (fNIRS) was used to measure changes of hemoglobin concentrations in prefrontal areas during the verbal fluency task (VFT) before and after stimulation. Results: After stimulation, iTBS to the left DLPFC with 70% RMT maintained the concentration change of oxyhemoglobin (HbO) in the target area during the VFT. In contrast, 50% [t (17) = 2.203, P = 0.042, d = 0.523] and 100% iTBS [t (17) = 2.947, P = 0.009, d = 0.547] significantly decreased change of HbO concentration, indicating an inverse U-shape relationship between stimulation intensity and prefrontal hemodynamic response in healthy young adults. Notably, improved VFT performance was only observed after 70% RMT stimulation [t (17) = 2.511, P = 0.022, d = 0.592]. Moreover, a significant positive correlation was observed between task performance and the difference in HbO concentration change in the targeted area after 70% RMT stimulation (r = 0.496, P = 0.036) but not after 50 or 100% RMT stimulation. Conclusion: The linear relationship between stimulation intensity and behavioral outcomes reported in previous conventional rTMS studies may not be translated to iTBS. Instead, iTBS at 70% RMT may be more efficacious than 100% RMT.