Neuroreport最新文献

Background: Perimenopausal depression (PMD), a psychiatric disorder triggered by declining ovarian function before menopause, remains poorly understood in terms of therapeutic mechanisms. While acupuncture has demonstrated efficacy in alleviating PMD symptoms, its molecular basis requires further exploration. This study aimed to investigate whether acupuncture ameliorates PMD by modulating phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (AKT)/mammalian target of rapamycin (mTOR) signaling in a rat model.

Methods: The female SD rats were randomly assigned to four groups: model, blank, acupuncture, and Western medicine, with each group consisting of six rats. The acupuncture group received acupuncture at the Baihui (GU20), Shenshu (BL23), Ganshu (BL18), and Sanyinjiao points for 28 consecutive sessions over 4 weeks. A PMD rat model was established through ovariectomy (OVX) combined with chronic unpredictable mild stress. Depression-related behaviors were measured through the forced swimming test, sucrose preference test, and open field test. The levels of estrogen (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and gonadotropin-releasing hormone (GnRH) in serum were determined through ELISA. The expression of PI3K, AKT, and mTOR in the hippocampal Cornu Ammonis 1 (CA1) region was analyzed by reverse transcription quantitative PCR and Western blotting.

Results: Acupuncture markedly attenuated depression-like behaviors and hippocampal pathology in PMD rats. It restored hormonal balance by elevating serum E2 while suppressing FSH, LH, and GnRH. At the molecular scale, acupuncture enhanced the expression of both mRNA and proteins of PI3K, AKT, and mTOR in the hippocampus CA1 region.

Conclusion: Acupuncture alleviates PMD through dual regulation of sex hormone homeostasis and activation of the PI3K/AKT/mTOR pathway, suggesting a potential mechanism for its antidepressant effects in perimenopause.

Objectives: Accumulating evidence indicates distinct differences in static brain activity between eyes-open (EO) and eyes-closed (EC) resting states. However, whether dynamic alterations in intrinsic brain activity are significantly associated with ocular states remains unsubstantiated. This study aimed to investigate state-dependent modulations of dynamic intrinsic brain activity across EO and EC conditions through dynamic amplitude of low-frequency fluctuation (dALFF) - a methodological framework integrating conventional amplitude of low-frequency fluctuation metrics with sliding-window analytical approaches.

Methods: A cohort of 26 subjects (13 males and 13 females) was demographically matched by age, sex, and educational attainment. The dALFF values across brain regions were calculated for both EO and EC states using sliding-window analysis, with subsequent comparison of dynamic brain activity between these ocular conditions.

Results: Relative to the EC condition, the EO state exhibited reduced dALFF values in the left Parietal Inf. Conversely, elevated dALFF values were observed in the left Cerebellum 6, left Fusiform, the left and right Occipital Mid, and right Precentral during EO compared to EC.

Conclusion: Our principal findings revealed significantly heightened neural activity in the left Cerebellum 6, left Fusiform, the left and right Occipital Mid, and right Precentral during EO compared to EC resting states. Conversely, diminished dALFF was identified in the left Parietal Inf under EO conditions. These differential activation patterns collectively suggest that intrinsic brain dynamics are substantially modulated by visuomotor state transitions, particularly involving ocular status alterations.

Background: Peripheral nerve injury (PNI) leads to substantial functional impairment, yet current therapies remain limited. Electroacupuncture (EA) is a promising intervention for PNI, but its mechanisms, particularly its role in modulating energy metabolism during nerve regeneration, are poorly understood.

Methods: A mouse PNI model was established by crushing the right sciatic nerve. EA stimulation was applied on the right side acupoints of Huantiao (GB30) and Zusanli (ST36) in PNI mice. Hind-limb splaying and gait analysis were used to evaluate motor function, and electrophysiological tests were used to assess nerve conduction. Nerve regeneration and molecular mechanisms were examined by Western blot, immunofluorescence, and transmission electron microscopy.

Results: We found that EA treatment significantly improved motor function, increased compound muscle action potential amplitude, and reduced muscle atrophy. Axonal regeneration was accelerated, as evidenced by increased SCG10-positive fibers. EA increased mitochondrial transcription factor A, mitochondrial DNA copy number, and mitochondrial electron transport chain activity, indicative of improved mitochondrial function and oxidative phosphorylation. Moreover, EA was identified to enhance energy metabolism by upregulating neurotrophic factors and modulating the AMPK/mTOR/p70S6K pathway.

Conclusion: Our findings indicate that EA at Huantiao (GB30) and Zusanli (ST36) promotes nerve regeneration and functional recovery after PNI by upregulating energy metabolism. This study provides a novel perspective on the therapeutic potential of EA in peripheral nerve repair.

Background: Prenatal alcohol exposure (PAE) is recognized as the leading cause of adverse prenatal exposure disorders worldwide. The neurodevelopmental impairments resulting from PAE in offspring are classified under fetal alcohol syndrome (FAS). Nonetheless, the precise underlying pathogenic mechanisms of FAS remain incompletely understood, and effective therapeutic interventions are currently lacking. Notably, the antioxidant astaxanthin has demonstrated significant neuroprotective properties.

Methods: In this study, we established a C57BL/6J mouse model of FAS and administered potential therapeutic doses of astaxanthin through oral gavage. We evaluated the dual effects of ethanol exposure and astaxanthin intervention on oxidative stress, cognitive development, and cellular apoptosis in FAS. Furthermore, using molecular detection and plasmid transfection, we validated the regulatory cascade between the transcription factor Maf and the antiapoptotic protein B-cell lymphoma 2 (Bcl2), demonstrating the therapeutic efficacy and mechanism of astaxanthin against FAS.

Results: The results demonstrate that prenatal alcohol exposure induces neuronal oxidative damage and cognitive developmental impairments, concomitant with reduced expression of the transcription factor Maf in the brain and consequent suppression of antiapoptotic Bcl2 activity. Strikingly, astaxanthin administration significantly attenuated alcohol-induced reactive oxygen species accumulation and restored both Maf and Bcl2 expression levels. This intervention effectively ameliorated neuronal apoptosis and neurodevelopmental abnormalities.

Conclusion: These findings reveal that astaxanthin alleviates FAS-related pathophysiology by rescuing the alcohol-disrupted Maf-Bcl2 axis, consequently reducing neuronal cell death. This study provides novel mechanistic insights into FAS pathogenesis and identifies a promising therapeutic strategy.

Objective: The visual cortex plays a crucial role in integrating multiple stimulus features, such as orientation tuning and spatial frequency tuning , to form coherent perceptual representations of the visual environment. Although previous research has hinted at the presence of overlapping maps for orientation and spatial frequency tuning in the visual cortex, clear evidence demonstrating how these features are jointly organized functionally is scarce.

Methods: To address this, we performed multiunit electrophysiological recordings in the primary visual cortex (V1) of anesthetized cats. We presented visual stimuli consisting of drifting sine-wave gratings under two experimental conditions: varying the orientation while keeping spatial frequency constant and varying spatial frequency while maintaining fixed orientations at 0° or 90°. Neuronal responses were analyzed by fitting tuning curves to quantify preferred orientations and spatial frequencies. Functional connectivity between neurons was then assessed using cross-correlogram analysis.

Results: Our results showed that neurons with similar orientation and spatial frequency tuning, exhibited significantly stronger connectivity at 0° orientation, whereas this effect was not observed at 90°. These results indicate that the organization of neuronal networks in V1 is stimulus-dependent and that overlapping ensembles encode these features in a coordinated manner. These results are important for understanding how complex features are integrated within the visual system, and more broadly, how the brain processes and combines information.

Conclusion: Such feature-based connectivity likely enhances the visual cortex's ability to efficiently process complex stimuli, supporting the idea that perceptual integration relies on the dynamic interplay of neurons sharing similar tuning properties.

Objective: This study explores the changes in functional connectivity density (FCD) among patients with diabetic retinopathy and its associations with gene expression and the distribution of neurotransmitter density, aiming to elucidate potential pathophysiological mechanisms underlying diabetic retinopathy.

Methods: This study investigates changes in short-range functional connectivity density (sFCD) within regions and long-range functional connectivity density (lFCD) between regions in 46 patients with diabetic retinopathy compared with 46 healthy controls. In addition, we examine the relationship between FCD changes in patients with diabetic retinopathy and whole-brain gene expression through partial least squares (PLS) regression and functional enrichment analysis of PLS-weighted genes. Finally, we assess the spatial correlation between abnormal FCD patterns and neurotransmitter density distribution using correlation analysis.

Results: The patients with diabetic retinopathy show a reduction in lFCD in the left inferior occipital gyrus and in the cortex surrounding the left calcarine fissure (left Cal) and a significant decrease in sFCD in the left Cal and the supplementary motor area (SMA). Furthermore, FCD is significantly positively correlated with the PLS1 gene and exhibits notable associations with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Finally, the abnormal FCD patterns in patients with diabetic retinopathy demonstrate a significant spatial correlation with the density of 5HT1A and CB1 receptors.

Conclusion: In summary, patients with diabetic retinopathy have different degrees of abnormal brain connectivity function in vision-related and SMA regions, and this abnormal performance may be related to the high oxidative stress state and neurovascular abnormalities present in patients with diabetic retinopathy.

Objective: To investigate gray-white matter injury in heatstroke using multimodal MRI, and precisely localize damaged white matter segments via automated fiber quantification (AFQ) with clinical correlation.

Results: Compared with the healthy control group, VBM revealed reduced volume in bilateral cerebellar anterior lobes and left fusiform gyrus. TBSS showed widespread white matter abnormalities. AFQ identified: (a) Decreased fractional anisotropy in left corticospinal tract and right inferior fronto-occipital fasciculus; (b) increased mean diffusivity in left thalamic radiation, bilateral corticospinal tracts, corpus callosum forceps minor, bilateral inferior fronto-occipital fasciculus, left inferior longitudinal fasciculus, right superior longitudinal fasciculus, and bilateral uncinate fasciculi (false discovery rate - P  < 0.05). Specific nodes in the left thalamic radiation, right corticospinal tract, right inferior fronto-occipital fasciculus, left inferior longitudinal fasciculus, and left uncinate fasciculus were correlated with Glasgow Coma Scale and coagulopathy markers.

Conclusion: Heatstroke involves cerebellar/cortical atrophy and segment-specific white matter damage, where AFQ-precise localization links microstructural alterations to clinical severity and coagulopathy.

Objective: This study investigated whether parameter-optimized paired associative stimulation (PAS) could enhance neurological recovery after cerebral ischemia by modulating oxidative stress and inflammation in a rat middle cerebral artery occlusion (MCAO) model.

Methods: Twenty-four Sprague-Dawley rats were randomly divided into Sham, Model, PAS-ISI-10 ms, and PAS-ISI-15 ms groups. The MCAO model was established using the intraluminal filament method. PAS intervention (90 paired pulses/day for 28 days) was initiated 24 h postischemia. Neurological function was assessed using Longa scores, grip strength, and corner tests. Cerebral infarction (TTC staining), neuronal survival (Nissl staining), apoptosis (TUNEL), neuroregeneration markers (GAP43, BDNF, MAP2, and Syn), oxidative stress (GSH-Px and MDA), and inflammatory cytokines (IL-1β, IL-6, and TNF-α) were evaluated.

Results: The PAS-ISI-10 ms group demonstrated significantly better neurological recovery than PAS-ISI-15 ms ( P  < 0.05), with reduced infarct volume ( P  < 0.01) and lower apoptosis rates ( P  < 0.01). Neuroregenerative markers showed greater upregulation in the 10 ms group ( P  < 0.05). Oxidative stress markers were significantly improved in PAS groups (GSH-Px increased P  < 0.01; MDA decreased P  < 0.01), with more pronounced effects in the 10ms condition. Proinflammatory cytokines were markedly reduced in both PAS groups ( P  < 0.05), showing stronger suppression in the 10ms group.

Conclusion: Parameter-optimized PAS with 10-ms ISI promotes neurological recovery after cerebral ischemia through coordinated antioxidant, anti-inflammatory, and neuroregenerative mechanisms. These findings provide evidence for optimizing noninvasive neuromodulation strategies in stroke rehabilitation.

Background: Emerging evidence suggests that blood-oxygen-level-dependent signals in white matter reflect functional activity; however, it remains unclear whether white matter function is altered in rhegmatogenous retinal detachment (RRD) and how it interacts with gray matter.

Methods: We conducted resting-state functional MRI analyses in patients with RRD and healthy controls to investigate regional white matter activity using amplitude of low-frequency fluctuations/fractional ALFF (ALFF/fALFF), and cross-tissue white matter-gray matter functional connectivity. Voxel-wise analyses were performed to identify aberrant white matter regions, and seed-based connectivity mapping was applied using affected white matter tracts. Support vector machine models were constructed to evaluate the diagnostic utility of these functional features.

Results: Patients with RRD exhibited significantly increased ALFF/fALFF in key projection fibers, including the bilateral anterior corona radiata (ACR) and anterior limb of the internal capsule (ALIC). Enhanced functional connectivity was observed between the left ACR and nonvisual gray matter regions such as the right middle temporal gyrus and medial orbitofrontal cortex. Among all features, the fALFF value of the left ALIC demonstrated the highest classification performance (area under the curve = 0.8974) in distinguishing RRD from healthy controls.

Conclusion: These findings reveal aberrant spontaneous low-frequency oscillatory activity and enhanced white matter-gray matter coupling in patients with RRD, reflecting cross-tissue functional reorganization beyond the retina. Notably, the elevated fALFF signal in the left ALIC demonstrates strong potential as a neuroimaging biomarker. This study underscores the value of white matter functional metrics in characterizing central nervous system alterations in RRD and offers novel insights into its neurobiological underpinnings.