Frontiers in Neuroscience最新文献

Background: Gut dysbiosis is hypothesized to be a potential pathological mechanism in patients across the Alzheimer's disease (AD) spectrum. Nevertheless, despite growing interest, existing findings remain largely inconsistent.

Purpose: This systematic review and meta-analysis aimed to compare the composition of gut microbiota (GM) between patients with mild cognitive impairment (MCI) or AD and healthy controls (HC).

Methods: PubMed, Embase, MEDLINE and Web of science were searched from January 2022 to November 2025. Eligible studies included observational studies and pre-intervention arms of interventional trials reporting GM abundance in AD spectrum patients vs. HC. Two reviewers independently screened articles, extracted data, and assessed bias risk. Effect sizes were pooled using an inverse-variance weighted random-effects model.

Results: Twenty studies (1,025 HC and 456 AD spectrum patients) were analyzed. AD patients demonstrated reduced GM diversity vs. HC cohort. The abundances of Megamonas and Bacteroides were elevated in AD patients, while Firmicutes and Proteobacteria were reduced. When stratified by clinical stage, Fusobacteria and Lactobacillus abundances showed gradient shift from MCI to AD.

Conclusion: Individuals within the AD spectrum exhibit altered GM abundance, with these differences influenced by clinical stage. The present study did not identify any significant trends; it reports only findings that have been statistically substantiated.

Circadian rhythms orchestrate nearly all physiological and behavioral functions, and their deterioration with aging contributes to sleep disruption, cognitive decline, and increased vulnerability to disease. Melatonin, the primary hormonal signal of darkness, plays a central role in maintaining circadian synchrony, regulating sleep, and exerting antioxidant and neuroprotective effects. This review provides an integrative synthesis of current evidence on the multi-layered role of melatonin in aging, encompassing molecular, neurobiological, behavioral, and nutritional dimensions. Aging alters the circadian system, particularly melatonin secretion, amplitude, and receptor sensitivity, and these changes affect sleep architecture, metabolism, and cognitive function. Melatonin depicts pleiotropic actions as a circadian synchronizer, sleep facilitator, mitochondrial protector, immunomodulator, and neuroprotective agent. Evidence suggests that age-related melatonin decline contributes to "accelerated" aging through increased oxidative stress, mitochondrial dysfunction, and inflammatory burden ("inflammaging"), whereas restoring melatonin levels, via supplementation or diet, may mitigate such processes. In parallel, we address the emerging field of chrononutrition, emphasizing that the timing of food intake and consumption of melatonin-rich or polyphenol-containing foods can enhance circadian rhythmicity, improve sleep quality, and reduce age-related metabolic and oxidative stress. Melatonin decline represents both a biomarker and mediator of circadian aging. Integrating chronobiological and nutritional interventions, including timed melatonin supplementation, dietary chronobiotics, and lifestyle alignment with the light-dark cycle, holds promise for preserving circadian integrity, delaying physiological aging, and extending health span. Forthcoming research should focus on personalized chronotherapy and nutritional chronobiology to better harness melatonin's therapeutic potential in aging populations.

Introduction: The adhesion G Protein-Coupled Receptor 110 (GPR110) is highly expressed in brain during development. Although its level is broadly reduced in adulthood, GPR110 expression notably persists in the hippocampus, yet its role in adult neurobehavioral function remains incompletely defined. In this study, we investigated whether altering GPR110 levels affects behavior and associated molecular pathways in adult mice.

Methods: Using mice with global deletion of GPR110 and mice with Cre-dependent overexpression of GPR110 in glutamatergic neurons, we performed behavioral testing and transcriptomic and proteomic analyses of hippocampal and cortical tissue.

Results: Global deletion of GPR110 led to increased immobility in the open field test and impaired learning and memory, accompanied by downregulation of genes and proteins involved in synaptogenesis, neurotransmission, glutamatergic signaling, and neuronal development. In contrast, overexpression of GPR110 selectively in glutamatergic neurons reduced anxiety- and compulsive-like behaviors with enhanced receptor-mediated signaling and proteins linked to neuronal morphogenesis and synaptic communication.

Discussion: Together, these findings demonstrate that GPR110 regulates anxiety-related and cognitive behaviors in adult mice and modulates synaptic and signaling pathways that support neuronal structure and communication. The GPR110-dependent mechanism as a new target for neurobehavioral modulation may provide a strategy to mitigate anxiety- and cognition-related pathophysiologic behavioral conditions.

[This corrects the article DOI: 10.3389/fnins.2025.1484954.].

Sensory decline is a common feature of aging and an early sign of a high risk of developing neurodegenerative diseases. Abnormal protein deposits of tau are also observed in sensorial areas in early stages of Alzheimer's disease and related dementia (ADRD), indicating that these two features are associated with common neuropathological changes in the affected brain areas. Alterations in taste and smell are evident in subjects with cognitive decline, but sensory decline is perceived in olfaction, vision, hearing (at early times of degeneration), and even touch, which correlates with disease progression. Consequently, affected individuals may suffer from varying altered behaviors that emerge from the declined capability to process and perceive information, suggesting that differences in sensory perception of the environment may play a key role in explaining these behavioral variations in subjects with cognitive impairment. This commentary discusses some of the alterations in sensory functionality and how these could contribute to the development of neurodegenerative disorders, such as ADRD.

Objective: Studies have shown that the pathophysiological mechanisms of Chronic neck and shoulder pain (CNSP) involve not only local spinal and neural abnormalities but also abnormal brain cortical structures related to pain modulation. However, it remains unclear how these cortical alterations may influence efficacy of treatment.

Materials and methods: 31 CNSP patients and 30 age- and gender-matched healthy controls (HCs) underwent 3D high-resolution structural magnetic resonance imaging (MRI) scans. The CNSP patients underwent a second MRI scan 3 months after receiving minimally invasive interventional treatment. The longitudinal changes in cortical thickness (CT), fractal dimension (FD), gyrification index (GI), and sulcal depth (SD) were studied before and after treatment in the CNSP patients, and conducted partial correlation analysis with treatment efficacy.

Results: Compared to healthy controls, CNSP patients at baseline exhibited significant reduced cortical thickness (CT) in the bilateral precentral gyrus, superior frontal gyrus, lingual gyrus, left paracentral lobule, fusiform gyrus, superior temporal gyrus, supramarginal gyrus, and right precuneus. Deeper sulcal depth (SD) was observed in the bilateral central sulcus, anterior and posterior cingulate cortices, insula, lateral orbitofrontal cortex (OFC), and left dorsolateral prefrontal cortex (DLPFC). Additionally, an increased Gyrification Index (GI) was found in the bilateral lingual gyrus, left lateral OFC, anterior/posterior cingulate cortices, and right medial OFC. Three months after minimally invasive intervention, these morphological abnormalities showed widespread normalization. Correlation analyses revealed that higher baseline CT in the left precentral gyrus and paracentral lobule, lower baseline SD in the left cingulate cortex and central sulcus, and higher baseline GI in the right medial OFC were significant predictors of greater pain relief. Furthermore, the longitudinal restoration of CT in the left precentral gyrus and SD normalization in the left DLPFC and cingulate cortex were positively correlated with the reduction in VAS scores.

Conclusion: This study identifies specific morphological alterations characterized by cortical thinning and increased sulcal depth in the sensorimotor cortex (precentral gyrus, paracentral lobule, central sulcus) and the pain modulation network (cingulate cortex, DLPFC, OFC) as key biomarkers for CNSP. The findings demonstrate that baseline structural integrity in these specific regions serves as a robust predictor of treatment efficacy. Moreover, the longitudinal structural recovery paralleling pain relief confirms the reversible nature of maladaptive neuroplasticity, highlighting CT in the precentral gyrus and SD in the DLPFC as critical indicators for evaluating chronic pain interventions.

Introduction: Parkinson's Disease (PD) is diagnosed based on motor symptoms (bradykinesia, resting tremor, rigidity); yet non-motor symptoms such as sleep abnormalities, autonomic dysfunction, and cognitive changes often precede motor signs, fulfilling the criteria for prodromal PD. How motor and non-motor symptoms emerge from dopamine depletion and whether they involve separable neural substrates remains unclear.

Methods: We applied correlational tractography based on multi-shell, diffusion-weighted magnetic resonance imaging in early-stage PD to assess microstructural changes throughout the brain. Eight participants with early-stage PD and 5 healthy controls underwent motor, cognitive, and mood assessments, followed by structural and multi-shell, diffusion-weighted magnetic resonance imaging. Their groupwise differences in white matter integrity associated with PD status were quantified using correlational tractography, with and without age correction.

Results: Correlational tractography delineated both microstructural changes that held either a significant positive or negative association with PD status, where the statistical maps of these changes linked differentially to motor and non-motor symptoms. Quantitative anisotropy (QA) extracted from positively associated fibers significantly correlated with cognitive function, while QA of negatively associated fibers correlated with motor function-independent of the effect of age. Of note, QA of positively associated fibers correlated with depressive mood only in the age-uncorrected analyses, suggesting a strong age-related effect.

Conclusion: In early-stage PD, motor and non-motor symptoms are mapped to anatomically distinct pathways, suggesting separable pathophysiological mechanisms. These findings further suggest that correlational tractography is appropriate to evaluate changes in structural connectivity in neurodegenerative diseases and, potentially, their therapeutic interventions.

Background: Warsaw breakage syndrome (WABS) is a rare disease caused by mutations in the DDX11 gene. It is characterized by severe growth restriction, microcephaly, and sensorineural hearing loss, and reports of coexisting epilepsy are even rarer. There are no studies on the focused synthesis of epilepsy phenotypes in WABS.

Methods: A clinical review is conducted for a patient diagnosed with WABS. And a comprehensive search is performed using PubMed, Web of Science, and Scopus. We select only papers that report patients with WABS and epilepsy.

Results: We present a boy exhibiting the core manifestations of this syndrome. In addition to growth restriction, microcephaly, and sensorineural hearing loss, he has experienced recurrent epileptic seizures since 7 months of age. The child showed resistance to multiple antiepileptic drugs, with seizure types progressing from focal to epileptic spasms. Whole-exome sequencing identified two variants in the patient's DDX11 gene: c.2120delT (p.F707Sfs*60) and c.1949-3C>T (splicing). A literature review identified a total of 7 previously reported children with WABS complicated by epilepsy, and we collected and summarized their clinical and genetic information.

Conclusion: We report a child with WABS whose main symptom was epilepsy. This case expands the known mutation spectrum of WABS and provides a comprehensive summary of clinical and genetic data for WABS patients presenting with epilepsy.