Neuroreport最新文献

Background: Mild traumatic brain injury (mTBI) commonly has long-term cognitive and functional consequences; however, it is not clear whether these adverse outcomes begin in the acute phase of mTBI and are associated with changes in brain morphology and function.

Methods: The current study used T1-weighted MRI to determine whether cortical thickness, gray matter volume (GMV), and morphological brain networks were altered in patients with mTBI within 7 days of injury, and to examine whether these changes were associated with postacute cognitive and emotional abnormalities. Adults aged 18-56 years with mTBI ( n  = 43) and healthy controls ( n  = 37) completed the cognitive, emotional evaluation, and MRI examination, during which patients with mTBI completed symptom reports. Cortical thickness and GMV were estimated using Computational Anatomy Toolbox 12. On this basis, a gray matter covariance network was constructed based on the cortical thickness.

Results: After false discovery rate (FDR) correction, groups differed significantly on the left parahippocampal gyrus and left orbital part of the superior frontal gyrus GMV (mTBI > controls), but no cortical thickness. The network topological properties were also changed in the acute stage of mTBI. The GMV abnormality was related to postacute cognitive and emotional changes in the mTBI group.

Conclusion: The results emphasize that adverse outcomes begin in the acute phase and that the left parahippocampal gyrus and left orbital part of the superior frontal gyrus and related brain network abnormalities may be potential neuroimaging biomarkers explaining acute cognitive and depressive symptoms.

Purpose of the research: This study aimed to explore the effects of exercise on sensorimotor recovery after stroke, neuroplasticity changes in the brain and spinal cord, and spinal cord compensation mechanisms.

Methods: A rat model of ischemic stroke was induced using the middle cerebral artery occlusion/reperfusion method. A T10 spinal cord injury (SCI) model was induced using a modified Allen procedure. The animals were randomly assigned into: Sham group (S), stroke group (M), stroke+SCI group (MS), stroke+exercise+SCI group (MSI), and stroke+SCI group (MI). Neurological function was assessed poststroke using the modified Neurological Severity Score (mNSS) and Garcia scores. Infarct volumes were evaluated using triphenyl tetrazolium chloride staining, and neuronal damage was assessed using Nissl staining. Tumor necrosis factor-α (TNF-α), interleukin (IL)-10, and IL-1β levels were measured using ELISA. Neuroplasticity markers [GAP43, PSD-95, synapsin I, and brain-derived neurotrophic factor (BDNF)] levels were analyzed using WB, IHC, and ELISA.

Results: Exercise improved neurological function in stroke rats, as evidenced by the enhanced mNSS and Garcia scores in the MS group compared to the M group. Exercise also alleviated neuronal damage, with the MS group showing higher neuron counts and more intact Nissl bodies than the M group. Exercise in the MS group downregulated inflammation (TNF-α down, IL-10 up) compared to the M group. Furthermore, exercise upregulated neuroplasticity markers and BDNF in both the brain and spinal cord. The beneficial effects of exercise on neurological recovery were diminished in the presence of SCI, as evidenced by the impaired recovery in the MSI group.

Conclusions: Exercise enhances stroke recovery by improving neuroplasticity, reducing inflammation, and highlighting the spinal cord's role in compensation. These findings suggest spinal cord-targeted therapies may improve rehabilitation outcomes.

Background: Subarachnoid hemorrhage (SAH) is a cerebrovascular disease with a very high disability and mortality rate, which brings a huge economic burden to society. It is reported that inhibition of forkhead box O3 (FOXO3) can alleviate brain edema and neuroinflammation after SAH. However, the role and mechanism of FOXO3 in regulating SAH progression need to be further studied.

Methods: Mouse microglia were treated with oxyhemoglobin (OxyHb) to build SAH cell model in vitro. Western blot was used to measure the protein levels of FOXO3, ubiquitin-specific peptidase 30 (USP30), embryonic lethal-abnormal vision like protein 1 (ELAVL1), and pyroptosis-related proteins. Cell proliferation was tested by cell counting kit 8 assay and 5-ethynyl-2' -deoxyuridine assay. Inflammatory factors were detected by ELISA, and cell polarization was evaluated using flow cytometry. Cell pyroptosis was assessed by detecting. Co-immunoprecipitation assay, immunofluorescence colocalization assay, and RNA immunoprecipitation assay were used to evaluate the interaction between FOXO3 and USP30 or ELAVL1.

Results: Downregulation of FOXO3 inhibited inflammation, M1 polarization, and pyroptosis in OxyHb-induced microglia. USP30 promoted FOXO3 expression through deubiquitination. USP30 knockdown suppressed inflammation, M1 polarization, and pyroptosis in OxyHb-induced microglia, and these effects were abolished by FOXO3 overexpression. Also, ELAVL1 interacted with FOXO3 to facilitate its mRNA stability. Meanwhile, USP30 increased FOXO3 expression to activate the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway.

Conclusion: USP30-mediated deubiquitination of FOXO3 contributed to OxyHb-induced microglia inflammation, M1 polarization, and pyroptosis, providing a novel target for the treatment of SAH.

Objective: This study seeks to investigate the roles and underlying mechanisms of cell cycle exit and neuronal differentiation 1 (CEND1) on Parkinson's disease.

Methods: Real-time quantitative PCR (RT-qPCR) was employed to assess the expression levels of CEND1 in peripheral blood samples of Parkinson's patients. A cell model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPP + )-induced Parkinson's disease was established in-vitro. 3-[4,5-Dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assays were used to evaluate the impact of CEND1 on the viability of SH-SY5Y cells induced by MPP + , while flow cytometry was used to assess apoptosis of these cells. The expression of oxidative stress and inflammatory factors in MPP + -treated cells was detected by ELISA. In addition, the effect of CEND1 on Parkinson's disease was interfered by an activator of the nuclear factor kappa B (NF-κB) pathway to clarify the relationship between CEND1 and the NF-κB pathway in a cell model of Parkinson's disease.

Results: CEND1 expression is markedly downregulated in patients with Parkinson's disease and cells of the Parkinson's disease model. Downregulation of CEND1-induced apoptosis, inhibited cell proliferation, and promoted expression of inflammatory factors in MPP + -treated cells; however, high expression of CEND1 inhibited MPP + -induced apoptosis, inflammatory factor release, and oxidative stress. In addition, CEND1 inhibited the activation of the NF-κB pathway induced by MPP + , and phorbol 12-myristate 13-acetate reversed the effect of CEND1 on Parkinson's disease.

Conclusion: CEND1 plays a protective role in the Parkinson's disease cell model by suppressing NF-κB signaling pathway activation, offering a potential target and foundation for the diagnosis and therapy of Parkinson's disease.

Objective: Microglia can be polarized into a proinflammatory M1 phenotype or an anti-inflammatory M2 phenotype. An excess of the M1 phenotype and a deficiency of the M2 phenotype are crucial to the pathological process of ischemic stroke, but the molecular mechanism is still unclear. Although several studies have confirmed the therapeutic effects of PNS (Panax notoginseng saponins) on ischemic stroke, the precise molecular mechanisms of these effects remain poorly understood. The aim of this study was to investigate the molecular mechanism of PNS influencing microglia polarization via hematopoietic progenitor kinase 1 (HPK1) signaling pathway regulation.

Methods: BV2 cells were pretreated with PNS or GNE-1858 (HPK1 inhibitor) and then polarization into M1- and M2-like phenotypes via lipopolysaccharide + interferon-gamma or interleukin (IL)-4, respectively. Detection of M1- and M2-like phenotypes by flow cytometry. The mRNA levels of tumor necrosis factor-alpha, L-1β, Arg1, and IL-10 were measured by real-time PCR. The phosphorylation levels of HPK1, nuclear factor kappa-B (NF-κB), and c-Jun N-terminal kinase (JNK) were detected by western blot.

Results: The phosphorylation levels of HPK1, NF-κB, and JNK gradually increased under the M1 polarization condition. Under the M2 polarization condition, the phosphorylation levels of HPK1, NF-κB, and JNK gradually decreased. Inhibition of HPK1 activity effectively inhibited the activation of NF-κB and JNK during M1 polarization. PNS can inhibit the activation of JNK and NF-κB by inhibiting the activity of HPK1, thereby inhibiting the polarization of M1-like phenotype and promoting the polarization of M2-like phenotype.

Conclusions: This research confirmed that PNS effectively inhibits M1 microglial polarization while stimulating M2 microglial polarization via HPK1, JNK, and NF-κB signaling pathway suppression.

Objective: Bupropion, a norepinephrine-dopamine reuptake inhibitor, is widely used as an antidepressant and smoking cessation aid. At high doses, it also inhibits pancreatic β-cell ATP-sensitive potassium (KATP) channels, inducing insulin secretion. KATP channels are also expressed in the brain, and their gain-of-function mutations cause neurological disorders such as developmental delay, epilepsy, and neonatal diabetes (DEND syndrome). This study investigates bupropion's effects on KATP channels in mouse hippocampal CA1 pyramidal neurons.

Methods: The effects of bupropion on neuronal activity were examined in mouse hippocampal CA1 neurons using electrophysiological techniques. Specifically, whole-cell patch-clamp recordings were performed to measure changes in action potential firing frequency and membrane potential in response to bupropion application. To investigate the potential binding mechanism of bupropion to the KATP channel complex, AlphaFold3, an artificial intelligence-based protein structure prediction tool, was utilized.

Results: Electrophysiology revealed that bupropion significantly increased action potential firing frequency and altered membrane potential. AlphaFold3-predicted bupropion binding poses within sulfonylurea receptor 1 's transmembrane domain 0 highlighted key interactions. These structural predictions provide a plausible molecular basis for bupropion's observed electrophysiological effects.

Conclusion: These findings suggest bupropion's potential as a therapeutic strategy for DEND syndrome's neurological manifestations. Further investigation into the precise mechanisms and clinical applicability of these findings is warranted.

Background: Electromyographic (EMG) activity of auricular muscles in humans has been shown to be sensitive to the direction of auditory stimuli. Specifically, transient auricular EMG responses are significantly influenced by the laterality (left or right) and anteriority (in or outside the visual field) of auditory stimuli. As these factors co-occurred in previous research, this study aimed to isolate their influence, specifically of anteriority.

Methods: EMG signals of several auricular muscles were recorded from 11 participants. Transient auditory stimuli were presented from central (0° and 180°) and lateralized positions behind the participants (±150°).

Results: As previously reported, ipsilateral responses were significantly larger than contralateral responses. Surprisingly, however, responses recorded when stimuli were presented from 180° were also significantly smaller than ipsilateral responses, and approximately as large as contralateral responses. Responses generated by stimuli originating from 0° were extremely small, or almost nonexistent.

Conclusion: The implication of these results is that the main driving force of these responses is the lateralization of the auditory stimuli, while the anteriority appears to be only a secondary, minor contributor in the absence of lateralization. This behavior of the vestigial pinna-orienting system could be interpreted as an attempt to aid sound localization when visual information is not available, by, for example, changing the frequency filter properties of the pinna or by introducing interaural level differences by reorienting one pinna. Future studies investigating the auriculomotor system should be aware that presenting transient stimuli from central locations at 0° or 180° could generate only minor responses.

Background: High-definition transcranial direct current stimulation (HD-tDCS) enhances cognitive function, but its mechanisms and neural basis in mild cognitive impairment (MCI) are unclear. This study investigated whether HD-tDCS modulates cognition in MCI patients and correlates with resting-state functional MRI (rs-fMRI) measured changes in spontaneous brain activity.

Methods: Forty-three patients with MCI were randomized to receive 10 sessions of active HD-tDCS targeting the left dorsolateral prefrontal cortex or sham stimulation. rs-fMRI assessed degree centrality (DC) changes before and after the intervention. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Paired t-tests, independent t-tests, and analysis of variance were used to analyze DC differences and group-by-time interactions, with age, gender, education, and head motion as covariates.

Results: The HD-tDCS group exhibited significant DC increases in the cerebellum, right inferior temporal gyrus, left middle temporal gyrus, right precentral gyrus, and left dorsolateral superior frontal gyrus, with decreases in the left operculum inferior frontal gyrus, left angular gyrus, left superior parietal gyrus, and right superior occipital gyrus (P < 0.05, AlphaSim corrected). Sham stimulation induced minimal DC changes. No significant MMSE/MoCA improvements occurred in either group (P > 0.05).

Conclusion: HD-tDCS selectively modulates key nodes of cognitive and motor networks in MCI, as demonstrated by targeted DC alterations. Despite the absence of MMSE/MoCA improvements, this network-specific neuromodulation indicates HD-tDCS engages disease-relevant functional circuits. Longer interventions and sensitive cognitive metrics may clarify clinical relevance.

Objective: This study aimed to investigate whether Maresin conjugates in tissue regeneration-1 (MCTR1) can alleviate remifentanil-induced hyperalgesia (RIH) by modulating the mitochondrial fission protein dynamin-related protein 1 (DRP1).

Methods: Pain behavioral tests were conducted 24 h before remifentanil infusion and at 4, 8, and 24 h postinfusion. The expression of DRP1 and NR2B was assessed by Western Blot (WB). Additionally, intrathecal injections of MCTR1 were administered to evaluate the effects on RIH development and progression. Behavioral tests were conducted, meanwhile, the levels of DRP1, NR2B in the spinal cord, superoxide, including malondialdehyde (MDA), glutathione, and reactive oxygen species (ROS) in the spinal dorsal horn were measured. Mitochondrial numbers were counted via transmission electron-microscopy.

Results: After remifentanil administration, rats exhibited mechanical allodynia and thermal hyperalgesia, along with an increase in spinal levels of DRP1 and NR2B. However, MCTR1-treated rats showed alleviation of remifentanil-induced mechanical and thermal hyperalgesia, accompanied by reduced NR2B expression. Notably, MCTR1 treatment also led to decreased DRP1 expression and mitochondrial fission, as well as reduced MDA content and ROS production.

Conclusion: MCTR1 exerts a preventive effect on RIH by modulating NR2B activity through the DRP1-mitochondrial-ROS pathway.

Objective: Puerarin, a bioactive isoflavone glycoside predominantly extracted from the root of the kudzu plant ( Pueraria lobata ), is a traditional Chinese medicinal herb widely used for centuries. Alcohol withdrawal-induced depression (AWIDD), a serious psychiatric disorder, is prevalent in society. This study aimed to investigate the role of puerarin in oxidative stress and cyclic AMP (cAMP)/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway in AWIDD, as well as the underlying mechanism.

Methods: An alcohol withdrawal rat model was established. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-px) were measured using commercial kits. The cAMP level was detected by ELISA. CREB and phospho-CREB protein levels were analyzed by Western blot. BDNF level was assessed by reverse transcription-quantitative PCR. Dot blot was used to assess the total N6-methyladenosine (m 6 A) level. The interaction between obesity-associated protein (FTO) and prostaglandin-endoperoxide synthase 1 (PTGS1) was examined through RNA immunoprecipitation and dual-luciferase reporter assays.

Results: Puerarin decreased oxidative stress and increased the cAMP, p-CREB, and BDNF levels. Besides, puerarin increased FTO-mediated m 6 A demethylation in alcohol withdrawal rats. FTO inhibition increased oxidative stress and decreased the activation of cAMP/CREB/BDNF signaling pathway. Mechanistically, FTO weakened the stability of PTGS1 mRNA via m 6 A demethylation. Overexpression of PTGS1 reversed the reduction in oxidative stress and the activation of the cAMP/CREB/BDNF signaling pathway induced by FTO overexpression.

Conclusion: Puerarin suppressed oxidative stress and activated the cAMP/CREB/BDNF signaling pathway in AWIDD via regulating FTO-mediated m 6 A demethylation.