Neural Plasticity最新文献

Exercise training plays a pivotal role in neural repair and secondary injury prevention following spinal cord injury (SCI) and is widely implemented in clinical rehabilitation. It induces adaptive changes and remodeling within the nervous system of SCI patients, thereby improving functional impairments. The mechanisms underlying this adaptive remodeling involve complex signaling pathways, with mechanosensation and mechanotransduction being indispensable. Mechanosensitive ion channels (such as Piezo channels) sense and transduce mechanical forces generated during exercise, triggering downstream biochemical reactions that regulate cellular functions and ultimately promote functional recovery. This review systematically synthesizes evidence from Piezo channel-related animal studies and clinical research, focusing on their role in reshaping the structure and function of the nervous system through exercise intervention post-SCI. The study aims to elucidate the molecular mechanisms by which Piezo channels mediate exercise-induced functional recovery after SCI, providing a theoretical foundation for developing precision exercise prescriptions to facilitate functional reconstruction and rehabilitation in patients.

Background: Resting-state functional magnetic resonance imaging (rs-fMRI) reveals diverse neural activity patterns in adolescent major depressive disorder (MDD) with nonsuicidal self-injury (NSSI; nsMDD). However, the reported results are inconsistent. The aim of this study was to conduct a meta-analysis to identify consistent patterns of brain activity alterations in adolescent nsMDD.

Methods: A systematic search was conducted across PubMed, Web of Science, Embase, Google Scholar, Wanfang, and CNKI for rs-fMRI studies that compared nsMDD patients with healthy controls (HCs), up to June 30, 2025. Significant cluster coordinates were extracted for comprehensive analysis. We utilized regional homogeneity (ReHo) and amplitude of low-frequency fluctuations (ALFFs) analyses. Activation likelihood estimation (ALE) was used to identify regions of aberrant spontaneous neural activity in adolescent nsMDD compared to HCs.

Results: Eight studies (249 adolescent nsMDD and 278 HCs) were included. The ALE meta-analysis revealed increased activity in the left lingual gyrus (LING; Brodmann area [BA] 18) in adolescent nsMDD compared to HCs (voxel size = 200 mm³; p < 0.05). Decreased activity was observed in the right posterior cingulate cortex (PCC; BA 29) in adolescent nsMDD compared to HCs (voxel size = 360 mm³; p < 0.05). Jackknife sensitivity analyses demonstrated robust reproducibility in five of eight tests for the left LING and in six of eight tests for the right PCC.

Conclusions: This meta-analysis confirms consistent alterations in specific brain regions in adolescent nsMDD, highlighting the potential of rs-fMRI to refine diagnostic and therapeutic strategies.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by Aβ-amyloid accumulation and cognitive decline. Despite extensive research, effective treatments remain elusive. Astrocytes, the most abundant glial cells, play a crucial role in synaptic transmission, neuronal excitability, and plasticity. In AD, astrocytes become reactive, exhibiting aberrant calcium signaling and altered neurotransmitter release, making them promising targets for disease-modifying therapies. To address this, we explored designer receptors exclusively activated by designer drugs (DREADDs), specifically the hM3D(Gq) receptor, which selectively modulates intracellular Ca²⁺ levels in astrocytes upon activation by clozapine-N-oxide (CNO). Using daily CNO administration in 8-month-old 5xFAD mice, we observed a significant enhancement of impaired long-term potentiation formation, accompanied by cognitive improvements in the fear conditioning (FC) and Morris water maze (MWM) tests. Additionally, anxiety levels and social preference deficits in 5xFAD mice were fully restored following astrocytic activity modulation. Importantly, this approach reduced Aβ-amyloid plaque burden and demonstrated a trend toward mitigating astrocytic reactivity, further highlighting its therapeutic potential. Our findings suggest that targeting astrocytic activity via Gq-coupled receptors represents a novel and promising strategy for AD treatment, offering a noninvasive and effective approach to mitigating disease progression.

Peripheral nerve injury (PNI) represents a prevalent clinical condition, often resulting from mechanical trauma or tumor resection, which frequently induces persistent sensory deficits, motor impairment, neuropathic pain, or paralysis. Consequently, substantial socioeconomic burdens are imposed on affected individuals. Autologous nerve transplantation is often considered the preferred approach for reconstructing peripheral nerve defects; however, this technique is associated with limitations including donor-site sensory loss, restricted graft length, and nerve mismatches. Recently, peripheral blood mononuclear cells (PBMCs) have emerged as a focal point in nerve regeneration research due to their accessibility, immunomodulatory properties, and neuro-reparative potential. Nevertheless, the precise mechanisms underlying PBMC-mediated nerve repair remain incompletely characterized, and their molecular pathways require further elucidation. This study explores the potential role of PBMCs in promoting peripheral nerve regeneration, with a particular focus on their regulation of retrograde brain-derived neurotrophic factor (BDNF) transport through modulation of Hook1 expression and associated molecular pathways. This research seeks to provide novel insights for PBMC-based therapeutic strategies and establish a theoretical foundation for clinical translation. Implementation challenges and translational prospects for PBMCs in nerve regeneration are also critically evaluated.

Cardiac arrest (CA)-induced global cerebral ischemia (GCI) in childhood often results in learning and memory deficits. We previously demonstrated in a murine CA and cardiopulmonary resuscitation (CA/CPR) mouse model that a cellular mechanism of learning and memory, long-term potentiation (LTP), is acutely impaired in the hippocampus of juvenile males, correlating with deficits in memory tasks. However, little is known regarding plasticity impairments in juvenile females. We performed CA/CPR in juvenile (P21-25) female mice and used slice electrophysiology and hippocampal-dependent behavior to assess hippocampal function. LTP and contextual fear were impaired 7 days after GCI and endogenously recovered by 30 days. LTP remained impaired at 30 days in ovariectomized females, suggesting the surge in gonadal sex hormones during puberty mediates endogenous recovery. Unlike juvenile males, recovery of LTP in juvenile females was not associated with BDNF expression. NanoString transcriptional analysis revealed a potential role of neuroinflammatory processes, and specifically Cd68 pathways, in LTP impairment and hormone-dependent recovery. This was confirmed with staining that revealed increased Cd68 expression in microglia within the hippocampus. We were able to restore LTP in ovariectomized females with chronic and acute PPT administration, implicating estrogen receptor alpha in recovery mechanisms. This study supports a mechanism of endogenous LTP recovery after GCI in juvenile female mice, which differs mechanistically from juvenile males and does not occur in adults of either sex.

Objective: There currently lacks the prognosis assessment of hypertensive intracerebral hemorrhage (HICH) with acute disorders of consciousness (DoC) after early rehabilitation (ER). The present study aims to investigate the outcomes of consciousness and neurological and cognitive functions in HICH patients with acute DoC intervened with ER via a retrospective cohort study with propensity score matching (PSM). Methods: A total of 265 eligible HICH patients with acute DoC admitted to the First Affiliated Hospital with Nanjing Medical University from January 2021 to December 2023 were retrospectively recruited. They were randomly divided into the ER group (n = 115) and the nonER group (n = 150) before PSM. After the PSM at a ratio of 1:1, 96 patients were allocated to each group. Baseline characteristics before and after PSM were compared between the ER group and the nonER group. Outcome measures included the duration of mechanical ventilation, and proportions of participants with an emergence to a conscious state (eMCS), 0-3 points of the modified Rankin Scale (mRS), and cognitive impairment. Results: Baseline characteristics were comparable between the ER group and the nonER group after PSM (p ≥ 0.05). An ER significantly shortened the duration of mechanical ventilation (9 days vs. 10 days, p=0.022). The neurological prognosis at 3 months of HICH combined with acute DoC was significantly improved by the ER, with a significantly higher proportion of participants grading 0-3 points of the mRS in the ER group than the nonER group (57.3% vs. 40.6%, p=0.021). Among 174 participants who restored consciousness at 3 months of onset, a significantly lower proportion of cognitive impairment was detected in the ER group than the nonER group (25.8% vs. 53.2%, p=0.002). Conclusion: An ER shortens the duration of mechanical ventilation and improves the neurological prognosis in HICH patients with acute DoC. Although the outcome of consciousness is unable to be improved, an ER does reduce the risk of residual cognitive dysfunction in HICH patients with acute DoC.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder. The pathology of this disease is based on two basic mechanisms: amyloid-beta (Aβ) and tau fibrillation. Many genes and mechanisms have been identified as the primary causes of AD in clinical settings, and there have been exciting developments in drug treatments. Several molecules and biological structures regulate the genome outside of the standard DNA function. As in many diseases, circular RNAs (circRNAs), microRNAs (miRNAs), and exosomes (EXOs), investigated from different aspects of AD, are useful for treatment and diagnosis. This review examines two biological elements regarding their roles in the Aβ-tau pathology of AD and their potential as treatment targets. Importantly, the activities of miRNAs that play a role in these processes were evaluated. Trial Registration: ClinicalTrials.gov identifiers: NCT04120493, NCT04969172, NCT04388982.

Glutamate excitotoxicity is considered as the etiology of stroke and neurodegenerative diseases, namely, Parkinson's disease (PD), Alzheimer's disease (AD), and others. Meanwhile, substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc), a pivotal site in regulating orofacial nociceptive transmission via Aδ and C primary afferent fibers, majorly utilize glutamate as the principal excitatory neurotransmitter. Fucoxanthin (FCX), a carotenoid pigment extracted from brown seaweed, possesses various pharmaceutical properties including neuroprotective effect in multiple neuronal populations. To date, the direct activity of FCX on the SG of the Vc has not been extensively clarified. Consequently, we investigated the effect of FCX on excitatory signaling mediated by ionotropic glutamate receptors (iGluRs), using the patch-clamp technique recorded from SG neurons of the Vc. Here, FCX directly acted on glutamate receptors independent of voltage-gated sodium channel and γ-aminobutyric acid (GABA)_A/glycine receptors in the voltage-clamp mode. Specifically, the N-methyl-D-aspartic acid (NMDA)- and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced responses but not the kainic acid receptor (KAR)-mediated response were suppressed by FCX in standard extracellular solution. Additionally, the inhibitory effect of FCX on NMDA currents was repeatable and concentration-dependent. The FCX blockade of NMDA-mediated excitotoxicity was associated with the modulation of Ca²⁺ response without affecting Na⁺ ions. The Ca²⁺-dependent fluorescence intensity of brain slice was reduced in the presence of FCX. Notably, FCX significantly attenuated the spontaneous firing activity of SG neurons. Altogether, these results reveal that FCX may protect SG neurons against glutamate excitotoxicity via primarily regulating Ca²⁺ response, thereby inhibiting the excitatory signaling induced by NMDA and AMPA receptors (AMPARs).

Alzheimer's disease (AD) is a complex neurodegenerative disorder with multifaceted pathogenesis, which has been extensively investigated, yet effective treatments remain lacking. Splicing factor proline and glutamine rich (SFPQ) is known to play a crucial role in neurodegenerative diseases, including antioxidant-related functions and regulating gene expression within brain neurons. However, the specific role of SFPQ in AD pathology is not well understood. In this study, an AD mouse model was established through lateral ventricular injection of amyloid-beta_1-42 (Aβ _1-42). Subsequently, adeno-associated virus was administered to overexpress SFPQ in the hippocampus of AD mice. The results demonstrate that SFPQ overexpression improves recognition and memory in AD mice, while reducing AD-related marker proteins such as amyloid precursor protein (APP) and Tau. Additionally, synaptic and memory-associated proteins, as well as antioxidant proteins like glutathione S-transferase (GST) and heme oxygenase-1 (HO-1), were upregulated. The ratio of antiapoptotic protein Bcl-2 to proapoptotic protein Bax also increased. Furthermore, phosphorylated phosphoinositide 3-kinase (p-PI3K)/PI3K and phosphorylated protein kinase B (p-AKT)/AKT ratios were elevated, indicating activation of the PI3K/AKT signaling pathway. These findings suggest that SFPQ may serve as a promising molecular target for the prevention and treatment of AD.