Background: Multiple sclerosis (MS) is a chronic, autoimmune disorder that culminates in severe motor and cognitive deficits. The progression of the disease is associated with inflammation and demyelination of the brain and spinal cord. Activation and proliferation of glia, including astrocytes and oligodendrocytes, in the brain are hallmarks. Persons with MS (PwMS) have significantly low levels of the neuropeptide [Met5]-enkephalin (Met5-Enk), also termed Opioid Growth Factor (OGF) that is an inhibitory growth factor and modulates cellular homeostasis. Treatment with low doses of naltrexone, an opioid antagonist that blocks the receptor OGFr, is reported to decrease inflammation, neutralize pro-inflammatory cytokine secretion, and stabilize disease progression. Intermittent blockade of OGFr with low doses of naltrexone stimulates serum enkephalin levels. In this investigation, brains of mice with experimental autoimmune encephalomyelitis (EAE) were treated with low dose naltrexone (LDN) or OGF/Met-Enk and examined for reactive astrocytes and oligodendrocytes. Methods: Female C57BL/6J mice were inoculated with myelin oligodendrocyte glycoprotein (MOG35–55) to induce EAE. At the initial appearance of clinical behavioral symptoms, mice were randomized to receive 10 mg/kg [Met5]-enkephalin (OGF/Met-Enk), 0.1 mg/kg naltrexone (LDN), or 0.1 mL phosphate-buffered saline (PBS) daily. At 35 days post EAE induction, mice were euthanized, and the brains were removed and prepared for immunohistochemistry. The corpus callosum, subventricular zone, and dentate gyrus were stained with glial fibrillary acidic protein (GFAP) and adenomatous polyposis coli protein (APC) antibodies to detect astrocytes and oligodendrocytes, respectively. Results: The number of reactive astroglia in EAE brains was elevated relative to the number in normal mouse brains. Daily treatment with OGF/Met-Enk reduced GFAP-positive cells in all 3 brain regions, and LDN reduced astrocyte number in the corpus callosum and subventricular zone. Astrocytes in treated EAE mice had process lengths that were comparable with those in normal mice, suggesting less reactivity. The numbers of oligodendrocytes in the corpus callosum of EAE+LDN mice were significantly reduced relative to EAE+PBS tissues. Conclusions: These results demonstrate quantitative changes in reactive glia in EAE mouse brains following treatment with OGF/Met-Enk and LDN and corroborate other studies showing that OGF/Met-Enk and LDN treatment increase plasma enkephalins, reduce inflammation and decrease pro-inflammatory cytokines.
Background: The rapid integration of smartphones into daily life has undeniably brought immense convenience, but it has also introduced challenges, particularly in the form of problematic smartphone use (often referred to as smartphone addiction). This form of behavioral dependence has been linked to significant impairments in physiological, psychological, and social domains. Methods: In this systematic review, we investigated the neural underpinnings of smartphone addiction through various brain imaging techniques, with a particular emphasis on studies employing functional near-infrared spectroscopy (fNIRS), electroencephalography (EEG), functional magnetic resonance imaging (fMRI), and complementary neurostimulation as well as neurophysiological methods. Relevant data were retrieved from major academic databases—including CNKI, PubMed, and Web of Science—using a thorough keyword-based search strategy. A total of 41 studies were analyzed and categorized according to their research methods, participant characteristics, targeted populations, and key findings. Results: We identified a consistent association between smartphone addiction and alterations in brain structure and activity, as well as its co-occurrence with a range of mental health challenges. Conclusion: These findings collectively underscore the pressing need for further research into the neurobiological mechanisms of smartphone addiction and the development of targeted interventions to mitigate its adverse effects. The PROSPERO Registration: CRD420261369691, https://www.crd.york.ac.uk/PROSPERO/view/CRD420261369691.
Background: Transcranial ultrasound stimulation (TUS) has been shown to modulate recovery from propofol anesthesia. Etomidate is also widely used as an anesthetic in clinical practice. Therefore, further investigation is needed to clarify whether TUS modulates thalamic neural electrical activity under etomidate anesthesia. Methods: In this study, we applied TUS to the paraventricular nucleus of the thalamus (PVT) in etomidate-anesthetized rats. Local field potentials (LFPs) from the PVT and electromyography (EMG) signals from cervical muscles were recorded to analyze anesthesia recovery time, time-frequency characteristics, power spectral density, and sample entropy (SampEn). Results: The recovery time from anesthesia was significantly shorter in the TUS group than in the sham group. TUS also induced significant changes in LFPs metrics during emergence, including: a significant decrease in mean absolute power (MAP) in the 4–8 Hz band and increases in the 30–60 Hz, 60–100 Hz, 100–140 Hz, and 140–200 Hz bands; a reduction in relative power (RP) in the 4–8 Hz band and elevations in the 30–60 Hz and 60–100 Hz bands; and a significant increase in SampEn across the 1–200 Hz frequency spectrum. Conclusion: TUS effectively modulated the relative power, mean absolute power, and SampEn of LFPs during the transition from anesthetized to awake states in etomidate-anesthetized rats.
Background: To assess whether resting-state electroencephalography (EEG) connectivity differs between high-intelligence individuals (MENSA members) and controls using graph-theory metrics: clustering coefficient, characteristic path length, and small-worldness. Methods: Resting-state 64-channel EEG data were recorded in 29 MENSA participants and 20 controls. Functional connectivity was estimated using Lagged Linear Coherence across delta, theta, alpha, and beta bands. Graph-theory measures were computed using sLORETA and the Brain Connectivity Toolbox. Between-group comparisons were performed using the Mann–Whitney U test; p-values were corrected for multiple comparisons using the Benjamini–Hochberg false discovery rate (FDR) procedure, and effect sizes with 95% confidence intervals were calculated. Results: Compared with controls, MENSA participants showed significantly lower characteristic path length in the alpha band (Benjamini–Hochberg (BH) critical value = 0.004), indicating greater global network integration. In the beta band, they showed a higher clustering coefficient (BH critical value = 0.008), reflecting greater local specialization; together with a higher characteristic path length (BH critical value = 0.013), suggesting reduced global communication. No significant group differences were observed in small-worldness across frequency bands. Conclusions: High-Intelligence Quotient (IQ) individuals show a frequency-dependent resting-state cortical organization, characterized by enhanced alpha-band integration and increased beta-band local specialization. These findings support a nuanced neural-efficiency model of intelligence without changes in small-world architecture. Given the cross-sectional and observational design, these findings should be regarded as associative rather than causal and require replication in larger, independent samples. These findings indicate frequency-specific differences in functional network organization, although their cognitive implications remain to be established.
Background: Neuronal ferroptosis following acute ischemic stroke (AIS) contributes to ischemic brain injury and is regulated by nuclear factor erythroid 2-related factor 2 (NRF2), a key regulator of antioxidant defense and iron homeostasis. Whether electroacupuncture (EA) suppresses neuronal ferroptosis by regulating NRF2 stability and nuclear translocation through upstream glycogen synthase kinase 3 beta (GSK-3β) remains unclear. We investigated whether EA inhibits neuronal ferroptosis and alleviates ischemic brain injury by modulating the GSK-3β/NRF2 axis. Methods: Middle cerebral artery occlusion/reperfusion (MCAO/R) models were established in C57BL/6 and conditional Nrf2-knockout mice. The GSK-3β inhibitor laduviglusib (CHIR-99021; CHIR), the ferroptosis inhibitor ferrostatin-1 (Fer-1), and conditional Nrf2 knockout were used to investigate the anti-ferroptotic mechanism of EA and the regulatory hierarchy between GSK-3β and NRF2. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, and immunofluorescence were used to examine the GSK-3β/NRF2 pathway and ferroptosis-related molecules. NRF2 nuclear localization, neuronal nuclei (NeuN) /acyl-CoA synthetase long-chain family member 4 (ACSL4) double immunofluorescence, and co-immunoprecipitation were used to assess NRF2 nuclear translocation, neuronal ferroptosis, and the GSK-3β–NRF2 interaction, respectively. Results: EA inhibited GSK-3β activity after MCAO/R, restored NRF2 protein expression, promoted nuclear accumulation, and upregulated NAD(P)H:quinone oxidoreductase 1 (NQO1). EA also downregulated ACSL4 and transferrin receptor 1 (TfR1), upregulated glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), reduced NeuN/ACSL4-colocalized neurons, decreased ferrous iron (Fe2+) and malondialdehyde (MDA) levels, and increased superoxide dismutase (SOD) activity, glutathione (GSH) content, and the GSH/oxidized glutathione (GSSG) ratio. CHIR and Fer-1 produced similar anti-ferroptotic effects, and co-immunoprecipitation confirmed GSK-3β–NRF2 interaction. Conditional Nrf2 knockout did not affect EA- or CHIR-mediated GSK-3β phosphorylation but markedly attenuated their effects on NQO1, SLC7A11, GPX4, and TfR1. EA also alleviated mitochondrial ultrastructural damage, reduced cerebral infarction and Fluoro-Jade B (FJB)-positive neurons, and improved neurological function and motor coordination in MCAO/R mice. Conclusion: These findings identify the GSK-3β/NRF2 axis as an important regulatory mechanism of regulating neuronal ferroptosis after MCAO/R and support EA as a potential therapeutic strategy for alleviating neuronal ferroptosis and cerebral ischemia-reperfusion injury through GSK-3β inhibition and NRF2 activation.
