Objective:This study aims to investigate the mechanism and potential effects of two exposures to 100 dB sound pressure level（SPL） broadband white noise, with a 14-days interval, on the myelin sheath of the cochlear auditory nerve in mice. The research provides experimental evidence for understanding the pathophysiological processes of noise-induced hearing loss and hidden hearing loss. Methods:Fifteen 6-week-old male C57BL/6J mice with normal hearing thresholds were randomly divided into three groups: a control group（no noise exposure）, a single noise exposure group, and a double noise exposure group. The single noise exposure group was exposed to 100 dB SPL white noise for 2 hours, and ABR thresholds were measured 1 day（P1） and 14 days（P14） after the exposure. The double noise exposure group was exposed to the same conditions of 100 dB SPL white noise for 2 hours, followed by a second identical exposure 14 days later. ABR thresholds were measured 1 day（P15） and 14 days（P28） after the second exposure. The cochleae of all three groups were then collected for immunofluorescence observation of the basilar membrane and transmission electron microscopy to observe changes in the structure of the auditory nerve myelin sheath. Results:In the single noise exposure group, ABR thresholds at all frequencies were significantly elevated compared to the control group at P1. There were no significant changes in ABR thresholds at any frequency at P14. In the double noise exposure group, ABR thresholds at all frequencies were significantly elevated compared to the control group at P15 and P28（P<0.001）. After the first noise exposure, immunofluorescence observation revealed no significant weakening of the auditory nerve myelin sheath signal; transmission electron microscopy showed no significant changes in myelin sheath morphology. However, after the second noise exposure, immunofluorescence observation revealed a weakening of the myelin sheath signal, and transmission electron microscopy showed thinning of the myelin sheath, disruption of the lamellar structure, and separation from the axon, indicating demyelination. Conclusion:Two exposures to 100 dB SPL broadband white noise can lead to damage to the auditory nerve myelin sheath in mice, whereas a single exposure does not cause significant changes.
Animals ; Male ; Myelin Sheath/pathology* ; Mice ; Cochlear Nerve/pathology* ; Mice, Inbred C57BL ; Noise/adverse effects* ; Hearing Loss, Noise-Induced/physiopathology* ; Cochlea ; Evoked Potentials, Auditory, Brain Stem

Objective:To investigate the impact of Waardenburg syndrome（WS） -associated Sox10 p.S100Rfs*9 mutation on inner ear function and its mechanism in noise-induced hearing impairment. Methods:A mice model carrying the Sox10 p.S100Rfs*9 mutation was established using CRISPR-Cas9 gene editing technology. Auditory phenotypes were assessed under baseline conditions and after noise exposure（96 dB SPL, 2 hours）. Auditory brainstem response（ABR） tests were performed to evaluate hearing function, combined with immunofluorescence staining of cochlear basilar membrane whole-mounts to observe hair cells and ribbon synapses. Transcriptome sequencing was conducted to analyze molecular mechanisms. Results:Sox10 p.S100Rfs*9 heterozygous mice exhibited normal hearing thresholds with characteristic ventral pigmentation abnormalities under baseline conditions. Following noise exposure, mutant mice showed significantly higher ABR thresholds at 24 000 Hz compared to wild-type controls（[60.00±6.12]vs[48.13±4.28]dB SPL, P<0.000 1）, and a significant reduction in ribbon synapses（CtBP2-positive puncta） in the basal turn（[55.0±2.3]vs[64.8±3.3]per inner hair cell, P=0.006 6）, while hair cell morphology and number remained intact. Transcriptome analysis revealed altered expression of genes involved in immune regulation, membrane structures, ion channels, and neuroactive ligand-receptor interactions. Conclusion:The Sox10 p.S100Rfs*9 mutation does not alter baseline hearing function but significantly increases inner ear susceptibility to noise damage, primarily manifested as enhanced ribbon synapse vulnerability, especially in high-frequency regions. This gene-environment interaction reveals that Sox10 haploinsufficiency may compromise noise tolerance by affecting synaptic stability and inner ear protective mechanisms. These findings provide new perspectives on the phenotypic heterogeneity in WS patients and theoretical basis for individualized noise protection strategies for patients carrying SOX10 mutations.
Animals ; SOXE Transcription Factors/genetics* ; Waardenburg Syndrome/physiopathology* ; Mice ; Hearing Loss, Noise-Induced/genetics* ; Evoked Potentials, Auditory, Brain Stem ; Mutation ; Noise ; Disease Models, Animal ; Ear, Inner/physiopathology*

OBJECTIVES: To evaluate the effect of eye acupuncture on neural function and angiogenesis of ischemic cerebral tissue in rats, and explore the roles of METTL3-mediated m⁶A methylation and the HIF-1α/VEGF-A signal axis in mediating this effect. METHODS: Fifty SD rats were randomized into normal control group, sham-operated group, model group, eye acupuncture group and DMOG (a HIF-1α agonist) group. Rat models of cerebral ischemia/reperfusion injury (CIRI) were established using a modified thread thrombus method, and the changes in neurological deficits of the rats after interventions were evaluated. TTC and Nissl staining were used to examine the changes in infarction size and neuronal injury, and cerebral angiogenesis was detected by double-immunofluorescence staining. m⁶A methylation modification level in the brain tissue was detected by ELISA, and RT-qPCR and Western blotting were used to detect the mRNA and protein expressions of METTL3 and HIF-1α/VEGF-A. RESULTS: Compared with the control and sham-operated rats, the CIRI rats had significantly higher neurological deficit scores with larger cerebral infarction area, a greater number of CD31- and EDU-positive new vessels, higher expression levels of HIF-1α and VEGF-A, reduced number of Nissl bodies and m6A methylation level, and lowered METTL3 protein and mRNA expressions. All these changes were significantly improved by interventions with eye acupuncture after modeling or intraperitoneal injections of DMOG for 7 consecutive days prior to modeling, and the effects of the two interventions were similar. CONCLUSIONS Eye acupuncture can improve neurological deficits in CIRI rat models possibly by promoting cortical angiogenesis via upregulating METTL3-mediated m⁶A methylation and regulating the HIF-1α/VEGF-A signal axis.
Animals ; Rats, Sprague-Dawley ; Methyltransferases/metabolism* ; Reperfusion Injury/physiopathology* ; Methylation ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Rats ; Vascular Endothelial Growth Factor A/metabolism* ; Brain Ischemia/metabolism* ; Acupuncture Therapy ; Male ; Up-Regulation ; Neovascularization, Physiologic ; Angiogenesis ; Adenosine/analogs & derivatives*

OBJECTIVES: To explore the effects of acupuncture combined with rehabilitation training for promoting transdifferentiation of astrocytes into neurons in mice after cerebral ischemia. METHODS: Male C57/BL6J mice were subjected to intracerebral microinjection of an adeno-associated virus carrying the GFAP promoter for NeuroD1 and Ngn2 overexpression in the astrocytes, followed 3 or 12 days later by electrocoagulation of the distal middle cerebral artery. After modeling, the mice were randomly divided into model group without interventions and intervention group treated with electroacupuncture at the acupoints Baihui (GV20), left Hegu (LI4), Neiguan (PC6), Zusanli (ST36), and Yanglingquan (GB34) 24 h after surgery. The mice in the intervention group were housed individually in cages with running wheels, and their activity was recorded every 24 h. Neurological function scores of the mice were assessed on the 1st, 14th, and 21st days after modeling. Transdifferentiation of astrocytes in the target brain regions was observed using double immunofluorescence staining. RESULTS: Compared with those in the model group, the mice receiving eletroacupuncture and rehabilitation training showed significant improvement of neurological deficits at 14 and 21 days after modeling. The GFAP promoter of the AAV2/5 vector specifically labeled the local astrocytes, and compared with that that in the model group, the number of AAV-positive cells colabeled with the neuronal marker DCX significantly increased after 14 days of electroacupuncture and rehabilitation intervention, and the number of AAV-positive cells colabeled with the neuronal marker NeuN significantly increased after 21 days of intervention. CONCLUSIONS In mice with cerebral ischemia, electroacupuncture and rehabilitation training can promote transdifferentiation of astrocytes into neurons in the ischemic brain region, and the efficiency of transdifferentiation is positively correlated with the improvement of motor function.
Animals ; Electroacupuncture ; Astrocytes/cytology* ; Cell Transdifferentiation ; Male ; Mice, Inbred C57BL ; Brain Ischemia/physiopathology* ; Mice ; Neurons/cytology* ; Doublecortin Protein

Depressive disorder is a chronic, recurring, and potentially life-endangering neuropsychiatric disease. According to a report by the World Health Organization, the global population suffering from depression is experiencing a significant annual increase. Despite its prevalence and considerable impact on people, little is known about its pathogenesis. One major reason is the scarcity of reliable animal models due to the absence of consensus on the pathology and etiology of depression. Furthermore, the neural circuit mechanism of depression induced by various factors is particularly complex. Considering the variability in depressive behavior patterns and neurobiological mechanisms among different animal models of depression, a comparison between the neural circuits of depression induced by various factors is essential for its treatment. In this review, we mainly summarize the most widely used behavioral animal models and neural circuits under different triggers of depression, aiming to provide a theoretical basis for depression prevention.
Animals ; Disease Models, Animal ; Depressive Disorder/psychology* ; Humans ; Behavior, Animal/physiology* ; Nerve Net/physiopathology* ; Brain/physiopathology* ; Neural Pathways/physiopathology*

Depression is increasingly prevalent among adolescents and can profoundly impact their lives. However, the early detection of depression is often hindered by the time-consuming diagnostic process and the absence of objective biomarkers. In this study, we propose a novel approach for depression detection based on an affective brain-computer interface (aBCI) and the resting-state electroencephalogram (EEG). By fusing EEG features associated with both emotional and resting states, our method captures comprehensive depression-related information. The final depression detection model, derived through decision fusion with multiple independent models, further enhances detection efficacy. Our experiments involved 40 adolescents with depression and 40 matched controls. The proposed model achieved an accuracy of 86.54% on cross-validation and 88.20% on the independent test set, demonstrating the efficiency of multimodal fusion. In addition, further analysis revealed distinct brain activity patterns between the two groups across different modalities. These findings hold promise for new directions in depression detection and intervention.
Humans ; Male ; Female ; Adolescent ; Case-Control Studies ; Depression/diagnosis* ; Early Diagnosis ; Rest ; Electroencephalography/methods* ; Brain-Computer Interfaces ; Models, Psychological ; Reproducibility of Results ; Affect/physiology* ; Photic Stimulation/methods* ; Video Recording ; Brain/physiopathology*

Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder influenced by both genetic and environmental factors, remains poorly understood regarding how its polygenic risk score (PRS) impacts functional networks and symptomology. This study capitalized on data from 11,430 children in the Adolescent Brain Cognitive Development study to explore the interplay between PRS_ADHD, brain function, and behavioral problems, along with their interactive effects. The results showed that children with a higher PRS_ADHD exhibited more severe attention deficits and rule-breaking problems, and experienced sleep disturbances, particularly in initiating and maintaining sleep. We also identified the central executive network, default mode network, and sensory-motor network as the functional networks most associated with PRS and symptoms in ADHD cases, with potential mediating roles. Particularly, the impact of PRS_ADHD was enhanced in children experiencing heightened sleep disturbances, emphasizing the need for early intervention in sleep issues to potentially mitigate subsequent ADHD symptoms.
Humans ; Attention Deficit Disorder with Hyperactivity/physiopathology* ; Male ; Female ; Sleep Wake Disorders/physiopathology* ; Adolescent ; Child ; Brain/diagnostic imaging* ; Multifactorial Inheritance ; Genetic Predisposition to Disease

Repetitive transcranial magnetic stimulation (rTMS) is a rapid and effective therapy for major depressive disorder; however, there is significant variability in therapeutic outcomes both within and across individuals, with approximately 50% of patients showing no response to rTMS treatment. Many studies have personalized the stimulation parameters of rTMS (e.g., location and intensity of stimulation) according to the anatomical and functional structure of the brain. In addition to these parameters, the internal states of the individual, such as circadian rhythm, behavior/cognition, neural oscillation, and neuroplasticity, also contribute to the variation in rTMS effects. In this review, we summarize the current literature on the interaction between rTMS and internal states. We propose two possible methods, multimodal treatment, and adaptive closed-loop treatment, to integrate patients' internal states to achieve better rTMS treatment for depression.
Humans ; Transcranial Magnetic Stimulation/methods* ; Depressive Disorder, Major/physiopathology* ; Neuronal Plasticity/physiology* ; Brain/physiopathology*

Previous studies have found associations between color discrimination deficits and cognitive impairments besides aging. However, investigations into the microstructural pathology of brain white matter (WM) associated with these deficits remain limited. This study aimed to examine the microstructural characteristics of WM in the non-demented population with abnormal color discrimination, utilizing Neurite Orientation Dispersion and Density Imaging (NODDI), and to explore their correlations with cognitive functions and cognition-related plasma biomarkers. The tract-based spatial statistic analysis revealed significant differences in specific brain regions between the abnormal color discrimination group and the healthy controls, characterized by increased isotropic volume fraction and decreased neurite density index and orientation dispersion index. Further analysis of region-of-interest parameters revealed that the isotropic volume fraction in the bilateral anterior thalamic radiation, superior longitudinal fasciculus, cingulum, and forceps minor was significantly correlated with poorer performance on neuropsychological assessments and to varying degrees various cognition-related plasma biomarkers. These findings provide neuroimaging evidence that WM microstructural abnormalities in non-demented individuals with abnormal color discrimination are associated with cognitive dysfunction, potentially serving as early markers for cognitive decline.
Humans ; White Matter/pathology* ; Male ; Female ; Cognitive Dysfunction/physiopathology* ; Middle Aged ; Aged ; Color Perception/physiology* ; Brain/pathology* ; Neuropsychological Tests ; Diffusion Tensor Imaging

Oxytocin is classically termed a 'prosocial neuropeptide' because of its evolutionarily conserved role in promoting affiliative behaviors. Endogenous oxytocin is mainly synthesized by hypothalamic oxytocin neurons and signals through oxytocin receptors (OxtRs). Recent studies with cell type-specific and circuit-specific interrogation have uncovered that oxytocin signals exert pleiotropic neuromodulatory effects through anatomically widespread axonal projections and ubiquitously distributed OxtRs. Dysfunctions of oxytocin signals are closely relevant to brain disorders/diseases. While intranasal oxytocin administration has been demonstrated to be one potential strategy to alleviate some brain disorders/diseases, such as autism, obesity, and anxiety, conflicting clinical outcomes highlight the imperative for precision-targeted neuromodulation strategies. Dissecting the molecular, cellular, and neural circuitry mechanisms underlying oxytocinergic modulation is a prerequisite to achieving this goal. This review provides an overview of the current understanding of the oxytocin system in terms of anatomical structure, neuronal modulation, and signal pathways, and discusses the modulatory roles of oxytocin in social, feeding, emotional, and sensory-related brain functions and brain diseases.
Oxytocin/metabolism* ; Humans ; Animals ; Hypothalamus/physiology* ; Brain/physiology* ; Brain Diseases/physiopathology* ; Receptors, Oxytocin/metabolism*