Brain and Behavior最新文献

Purpose: Autism spectrum condition (ASC) is a neurodevelopmental condition characterized by impairments in communication, social interaction, and restricted or repetitive behaviors. Extensive research has aimed to identify structural brain distinctions between individuals with ASC and neurotypical individuals using neuroimaging techniques. However, limited attention has been given to evaluating how variations in image acquisition protocols across different centers influence these observed differences.

Method: This analysis focuses on structural magnetic resonance imaging (sMRI) data from the Autism Brain Imaging Data Exchange I (ABIDE I) database, considering both subjects' condition and individual centers to identify disparities between ASC and control groups. Statistical analysis, employing permutation tests, utilizes two distinct statistical mapping methods: statistical agnostic mapping (SAM) and statistical parametric mapping (SPM).

Finding: Results from the SAM mapping method show greater consistency with existing literature. However, no statistically significant differences were found in any brain region. This outcome is attributed to factors such as limited sample sizes within certain centers, noise effects, and the challenges posed by multi-center databases in a heterogeneous condition such as autism.

Conclusion: The study indicates limitations in using the ABIDE I database to detect structural differences in the brain between neurotypical individuals and those diagnosed with ASC. Multi-center variability and sample size constraints significantly affect the reliability of findings in structural neuroimaging studies of autism.

Background: Intracerebral hemorrhage (ICH) induces severe neuroinflammation and microglial pyroptosis, exacerbating secondary brain injury. Rhein, a natural anthraquinone compound, possesses anti-inflammatory and neuroprotective properties. However, its effects on microglial pyroptosis and the underlying mechanisms remain unclear.

Methods: A rat microglial (RM) pyroptosis model was established using LPS + ATP induction, followed by rhein intervention and NLRP3 knockdown. Cell proliferation was assessed using CCK-8, and apoptosis was evaluated through TUNEL staining. ELISA was used to measure the expression levels of inflammatory cytokine. Immunofluorescence staining was performed to label M1/M2 microglia. RT-qPCR and western blot were used to analyze the expression of NLRP3, ASC, Caspase-1, GSDMD, PCNA, Cyclin D1, and CDK2. Transmission electron microscopy (TEM) was used to observe pyroptotic bodies. Additionally, a rat ICH model was established, with rhein intervention and NLRP3 knockdown/Caspase-1 inhibition. Behavioral assessments were conducted using the Y-maze test and open-field test. HE staining was performed to examine brain tissue pathology. ELISA was used to measure inflammatory cytokine levels in brain tissue. Immunofluorescence staining analyzed the distribution of M1/M2 microglia. RT-qPCR and western blot were used to detect pyroptosis-related proteins, and TEM was used to evaluate pyroptotic body formation.

Results: At the cellular level, rhein significantly promoted microglial proliferation and M2 polarization while inhibiting pyroptosis, inflammatory cytokine expression, M1 polarization, and NLRP3 expression. NLRP3 knockdown further enhanced the protective effects of rhein. At the animal level, ICH model rats exhibited reduced exploratory behavior, exacerbated neuroinflammation, increased pro-inflammatory cytokine expression, increased M1 microglia, and elevated NLRP3 expression and pyroptosis levels. Rhein intervention significantly alleviated inflammation in ICH rats by reducing the expression of NLRP3 and pyroptosis-related proteins. NLRP3 knockdown or Caspase-1 inhibition further enhanced rhein's protective effects.

Conclusion: Rhein alleviates neurological dysfunction following ICH by inhibiting NLRP3 inflammasome activation, reducing microglial pyroptosis, and mitigating neuroinflammation.

Background: Previous studies have suggested that adenosinergic system in the central nervous system may play a role in both behavioral changes and the physiopathology induced by Δ⁹-tetrahydrocannabinol (THC), and this is thought to be mediated by adenosine A₂A receptors (A₂ARs). However, the contribution of the adenosinergic system to the anxiety-like behaviors in response to THC in mice is not well understood.

Aims: In this study, we aimed to investigate the possible role of the adenosinergic system in THC-treated mice.

Methods: For that purpose, we combined behavioral tests and molecular analyses to investigate the effects of THC in relation with the agonist and antagonist of the adenosinergic system, CGS-21680 (CGS) and istradefylline, respectively, on both anxiety-like behaviors and hippocampal gene expression.

Results: The results demonstrated that THC induced anxiety-like behavior, and gene expression patterns indicated a significant interaction between the adenosinergic and cannabinoidergic systems. Notably, the data suggest that THC plays a predominant role in this molecular interplay, with its effects being partially modulated by changes in the expression of both cannabinoidergic and adenosinergic receptors, CB₁R and A₂AR, respectively.

Conclusion: These findings contribute to the understanding of THC's complex pharmacological actions, highlighting the importance of receptor cross talk in modulating anxiety and other behavioral outcomes.

Introduction: Depression is a chronic psychiatric disorder and belongs to one of the leading causes of suicide worldwide. Peroxiredoxins (Prdxs) play a critical role in scavenging excess reactive oxygen species (ROS) and mitigating oxidative stress. However, the role and underlying mechanisms of Prdxs in depression have not been fully illustrated.

Methods: We carried out lipopolysaccharide (LPS)-induced ICR depression mice and BV2 cell inflammation models. Seven days after LPS-induction, behaviors in ICR mice were assessed by open field test (OFT), sucrose preference test (SPT), and forced swim test (FST), and inflammatory factors levels in serum were quantified via ELISA. The expression levels of Prdxs were evaluated using immunohistochemistry (IHC), western blotting (WB), and RT-qPCR. In LPS-induced BV2 cells, inflammatory factor levels in the supernatant were measured by ELISA. Nitric oxide (NO) levels were detected by biochemical assay. ROS levels were detected via fluorescence signal intensity. Prdxs expression levels were analyzed using WB and RT-qPCR.

Results: In LPS-induced ICR mice serum and BV2 cells supernatant, interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta1 (TGF-β1) levels exhibited significant elevation (p < 0.05). In the hippocampus region of LPS-induced mice and LPS-induced BV2 cells, significant upregulation of Prdx1, Prdx2, Prdx4, and Prdx5 levels was observed (p < 0.05). The ROS and NO levels in LPS-induced BV2 cells also significantly increased (p < 0.05).

Conclusions: This study revealed that Prdx1, Prdx2, Prdx4, and Prdx5 were elevated in depression models, which might relate to the occurrence of neuroinflammation, coupled with upregulation of oxidative stress responses. This study provided new strategies for the treatment of depression.

Aims: The purpose of this review is to examine how epigenetic regulation particularly chromatin modification and histone methylation controls gene expression during embryonic neurogenesis. It aims to highlight the role of these mechanisms in neural stem cell (NSC) fate specification and their implications in neurological and neurodevelopmental disorders.

Methods: Through reviewing recent research findings, this study synthesizes current literature on epigenetic mechanisms involved in embryonic brain development, with a focus on histone modifications, chromatin remodeling, and chromatin compartmentalization. The review also evaluates existing in vivo research while noting the technical challenges of tracking adult neurons and isolating NSCs.

Findings: The review identifies that epigenetic mechanisms, including histone methylation (notably H3K9 as a repressive mark), histone deacetylases, and chromatin remodeling complexes, play essential roles in regulating gene expression required for neurogenesis and neuroplasticity. Alterations in these epigenetic processes significantly affect neural development and contribute to a range of neurological and neurodevelopmental disorders.

Conclusions: Understanding the epigenetic regulation of neurogenesis particularly through chromatin modification and structural chromatin dynamics provides valuable insight into cell fate determination during embryonic brain development. These insights may guide the development of novel therapeutic strategies for neurological and neurodevelopmental disorders.

Background: Inflammation in and around the brain in patients with meningitis can lead to confusion, cognitive dysfunction, and behavioral changes associated with mental health disorders. Stigma associated with HIV or mental illness can complicate meningitis, leading to misdiagnosis or delays in diagnosis and care. The frequency of misdiagnosis and/or co-occurrence of meningitis and mental illness among people living with HIV (PLWH) remains uncertain. We explored the experiences of meningitis patients and the barriers and facilitators to care related to HIV stigma and mental illness.

Methods: We conducted a convergent mixed-methods study to evaluate experiences of patients who were hospitalized with HIV-associated meningitis from February 2017 to May 2022 at Lira Regional Referral Hospital in Uganda. Experiences among patients who survived and family members of patients who died were explored. Surveys were conducted to obtain demographic information, investigate stigma, and assess symptoms of mental illness. Semi-structured interviews probed the overall experience of patients with HIV and meningitis regarding social support, mental health, and stigma.

Results: Twenty-four patients with HIV-associated meningitis and 20 family members of deceased meningitis patients were enrolled. Family members reported that 80% of deceased patients experienced stigma, whereas 29.2% of surviving patients reported experiencing stigma. Combined responses from surviving patients and family members identified 31.8% of patients with mental illness symptoms described as overthinking, depression, and/or anxiety, while 60.8% experienced HIV-related stigma. Among participants who died, family members reported mental illness symptoms in 40%, compared to self-reports of 25% in survivors. Barriers to HIV care included (a) lack of HIV education, (b) mental illness symptoms, (c) lack of social support, and (d) stigma or shame. While common facilitators were (a) access to HIV clinics and ART medication, (b) having a life purpose, and (c) social support.

Conclusion: Stigma and symptoms of mental illness were common among patients with HIV and meningitis, which likely affected antiretroviral therapy (ART) adherence and HIV care. Recommendations include (1) adding mental health screening during hospital admission for all meningitis patients, especially among PLWH, for early evaluation and treatment and (2) increasing community awareness to dispel misconceptions and reduce HIV-related stigma.

Background: Rotator cuff tendinopathy (RCT) is a major contributor to over 30 million surgeries which are conducted to treat shoulder overuse injuries worldwide annually. Accumulating evidence indicates that neuropsychiatric disorders (ND) share pathogenic pathways with tendinopathy. However, unclarified causal relationships between these two disease spectra undermine the individualized design of treatment strategies benefiting patients with ND while minimizing the RCT risk. We aimed to unveil whether ND were genetically associated with increased RCT occurrence by conducting a two-sample Mendelian randomization (MR) algorithm.

Methods: Genome-wide association studies (GWAS) data of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), epilepsy, major depressive disorder (MDD), obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), schizophrenia (SCZ), and RCT patients of European ancestry were retrieved for bidirectional two-sample Mendelian randomization (MR) analyses to establish causal relationships among these eight main types of ND and RCT. To detect false positive findings, MR-Egger, weighted median and causal analysis using summary effect estimates (CAUSE) were employed as sensitivity tests. Body shape, lifestyle, and socioeconomic parameters were adjusted as mediators in multivariable MR to validate the robustness of the results.

Results: Univariable MR revealed that genetic predisposition to ADHD (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.05-1.24, p = 0.001) and PTSD (OR 2.23, 95% CI 1.75-2.84, p < 0.001) significantly increased the RCT risk. MDD showed a similar association (OR 1.21, 95% CI 1.06-1.38, p = 0.004), which was attenuated after confounder adjustment (p = 0.78). Multivariable MR confirmed ADHD (OR 1.09, 95% CI 1.01-1.18, p = 0.02) and PTSD (OR 2.00, 95% CI 1.41-2.82, p < 0.001) as robust causal factors for RCT after adjusting for anthropometric, lifestyle, physical activity, and socioeconomic confounders.

Conclusion: Our study sheds new light on the need for early screening, targeted overuse injury prevention, and specialized clinical interventions to alleviate the RCT burden in ADHD and PTSD populations.

Introduction: Early identification of autism spectrum disorder (ASD) is critical for improving long-term outcomes, and speech offers a noninvasive source of clinically relevant biomarkers. However, manual speech analysis is time-consuming and difficult to scale. With advances in digital recording, signal processing, and artificial intelligence, researchers have increasingly deployed automated tools and data-mining methods to characterize speech and language in ASD.

Methods: This structured narrative review summarizes methodological developments in speech-based ASD assessment from 1994 to 2025, spanning diverse tasks and recording settings and focusing on automated tools, data-mining methods, and their clinical translation. We first consider core automated toolchains, including LENA, Praat, HTK/FAVE, CMU Sphinx, Kaldi, AutoSALT, openSMILE/eGeMAPS, diarization systems, and foundation-model ASR systems (e.g., Whisper), as well as modern self-supervised encoders such as wav2vec 2.0 and TRILLsson. Their typical use cases, psychometric properties, and limitations are highlighted. We then chart the progression of data-mining and machine-learning approaches from early logistic regression and clustering, through regularized regression, SVMs, and tree ensembles, to CNN/LSTM sequence models and transformer-based text and speech models (e.g., BERT, LLMs).

Results: Across these stages, automated indices of prosody, voice quality, linguistic content, and interactional behavior show moderate-to-high accuracy for ASD detection and meaningful associations with clinician-rated severity. Nonetheless, various problems persist: performance often degrades across languages, ages, tasks, and recording settings; evaluation and reporting remain heterogeneous; datasets are typically small and single-site; and privacy, fairness, interpretability, and computational efficiency pose persistent barriers to deployment, highlighting the need for target-context benchmarking and pre-specified evaluation/reporting.

Conclusion: We outline three priority strategies to guide future work toward scalable, clinically credible ASD speech assessment and longitudinal monitoring: optimize and integrate existing toolchains, enable global yet privacy-preserving data sharing, and leverage cross-domain innovations in enhancement, label efficiency, and explainable, edge-ready AI.

Background: Cognitive decline among the elderly is an increasingly prominent issue amid global population aging. Decanoic acid has been hypothesized to be associated with cognitive function. However, the relationship of decanoic acid with cognitive function in the elderly remains unclear.

Methods: This study analyzed the participants aged 60 years and older from National Health and Nutrition Examination Survey (NHANES) 2011-2014. Dietary decanoic acid (DDA) intake was derived from two 24-h dietary recalls. Cognitive function was assessed via immediate recall test (IRT), delayed recall test (DRT), animal fluency test (AFT), and digit symbol substitution test (DSST). Higher scores on these tests indicated better cognitive performance. Weighted multivariate linear regression, restricted cubic spline (RCS) curves, subgroup analyses, and mediating analysis were used to explore the relationship between DDA intake and cognitive function.

Results: A total of 2246 older adults were included in this study. After adjusting for confounding variables, DDA intake was positively associated with comprehensive cognitive function (β = 0.539, 95% CI: 0.168-0.910, p = 0.007). The RCS curve shows a positive correlation between DDA intake and comprehensive cognitive function (p-value for overall < 0.001, p-value for nonlinearity = 0.050). Subgroup analyses showed that the association remained relatively consistent across subgroups (all p for interaction > 0.05). Mediating analysis revealed that the indirect effects of hypertension and diabetes accounted for 27.53% and 24.33% of the total effect, respectively.

Conclusion: DDA intake is positively associated with global cognitive function in older adults. Hypertension and diabetes may partially mediate this relationship. The cross-sectional study design limits causal inference, and prospective or interventional studies should be conducted in the future.