Neural Plasticity最新文献

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.

Noise exposure is one of the most common causes of hearing loss and hyperacusis. Studies have shown that noise exposure can induce a cortical gain to compensate for reduced input of the cochlea, which may contribute to the increased sound sensitivity. However, many people with hyperacusis have no measurable cochlear lesion after being exposed to loud sound. In this experiment, we studied the neurological alterations in the cortical and subcortical areas following a prolonged moderate level of noise exposure (84 dB SPL, 8 h/day for 4 weeks) in the laboratory mice. The cochlear function was monitored by auditory brainstem responses (ABRs). The behavioral auditory sensitivity and temporal processing were evaluated using the acoustic startle response (ASR) and gap-induced prepulse inhibition (gap-PPI). The central auditory functions were determined by electrophysiological recordings of the inferior colliculus (IC) and the auditory cortex (AC). Our results showed that although there was no significant difference in the ABR thresholds, the noise group showed enhanced ASR and gap-PPI compared to the control group. Increased neural activity in both the IC and the AC was recorded in the noise-exposed mice compared to the control group, suggesting a central gain in both the subcortical and cortical regions. The current source density (CSD) analysis of the AC response revealed an increased columnar excitation and reduced corticocortical projection in the noise group, different from the central gain model of noise-induced hearing loss. Our results suggest that chronic "nondestructive" noise can increase the gain of the central auditory system by altering the balance of auditory thalamocortical and intracortical inputs, which may contribute to the increased sound sensitivity in people with normal hearing.

Objective: The investigation of brain functional network dynamics offers a promising approach to understanding network reorganization poststroke. This study aims to explore the dynamic network configurations associated with motor recovery in stroke patients and assess their predictive potential using multilayer network analysis. Methods: Resting-state functional magnetic resonance imaging data were collected from patients with subacute stroke within 2 weeks of onset and from matched healthy controls (HCs). Group-independent component analysis and a sliding window approach were utilized to construct dynamic functional networks. A multilayer network model was applied to quantify the switching rates of individual nodes, subnetworks, and the global network across the dynamic network. Correlation analyses assessed the relationship between switching rates and motor function recovery, while linear regression models evaluated the predictive potential of global network switching rate on motor recovery outcomes. Results: Stroke patients exhibited a significant increase in the switching rates of specific brain regions, including the medial frontal gyrus, precentral gyrus, inferior parietal lobule, anterior cingulate, superior frontal gyrus, and postcentral gyrus, compared to HCs. Additionally, elevated switching rates were observed in the frontoparietal network, default mode network, cerebellar network, and in the global network. These increased switching rates were positively correlated with baseline Fugl-Meyer assessment (FMA) scores and changes in FMA scores at 90 days poststroke. Importantly, the global network's switching rate emerged as a significant predictor of motor recovery in stroke patients. Conclusions: The reorganization of dynamic network configurations in stroke patients reveals crucial insights into the mechanisms of motor recovery. These findings suggest that metrics of dynamic network reorganization, particularly global network switching rate, may offer a robust predictor of motor recovery.

Although several adult rat models of medial temporal lobe epilepsy (mTLE) have been described in detail, our knowledge of mTLE epileptogenesis in infant rats is limited. Here, we present a novel infant rat model of mTLE (InfRPil-mTLE) based on a repetitive, triphasic injection regimen consisting of low-dose pilocarpine administrations (180 mg/kg. i.p.) on days 9, 11, and 15 post partum (pp). The model had a survival rate of >80% and exhibited characteristic spontaneous recurrent electrographic seizures (SRES) in both the hippocampus and cortex that persisted into adulthood. Using implantable video-EEG radiotelemetry, we quantified a complex set of seizure parameters that demonstrated the induction of chronic electroencephalographic seizure activity in our InfRPil-mTLE model, which predominated during the dark cycle. We further analyzed selected candidate genes potentially relevant to epileptogenesis using a RT-qPCR approach. Several candidates, such as the low-voltage-activated Ca²⁺ channel Ca_v3.2 and the auxiliary subunits β ₁ and β ₂, which were previously reported to be upregulated in the hippocampus of the adult pilocarpine mTLE model, were found to be downregulated (together with Ca_v2.1, Ca_v2.3, M₁, and M₃) in the hippocampus and cortex of our InfRPil-mTLE model. From a translational point of view, our model could serve as a blueprint for childhood epileptic disorders and further contribute to antiepileptic drug research and development in the future.

Hyperoside (Hyp), a kind of Chinese herbal medicine, exerts multiple therapeutic effects on many diseases. However, the role and mechanisms of Hyp in vascular pathophysiology in ischemic stroke need to be further established. The study aimed to investigate the role of (large-conductance Ca²⁺-activated K⁺) BK channels on the vasoprotection of Hyp against cerebral ischemia and reperfusion (I/R) injury in rats. The concentration gradient of Hyp was pretreated in both the middle cerebral artery occlusion and reperfusion model and oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary vascular smooth muscle cells (VSMCs) in rats. A series of indicators were detected, including neurological deficit score, infarct volume, malondialdehyde (MDA), superoxide dismutase (SOD), cerebral blood flow (CBF), cell viability, membrane potential, and BK channels α- and β1-subunits expression. The results showed that Hyp significantly reduced infarct volume and ameliorated neurological dysfunction in I/R-injured rats. Besides, the effects of I/R-induced reduction of BK channels α- and β1-subunits expression were significantly reversed by Hyp in endothelial-denudated cerebral basilar arteries. Furthermore, the protective effect against I/R-induced increases of MDA and reduction of SOD as well as CBF induced by Hyp was significantly reversed by iberiotoxin (IbTX). In OGD/R-injured VSMCs, downregulated cellular viability and BK channels β1-subunits expression were remarkably reversed by Hyp. However, neither OGD/R nor Hyp affected BK channels α-subunits expression, and Hyp failed to induced hyperpolarization of VSMCs. Moreover, the protective effect against OGD/R-induced reduction of cell viability and SOD level and increases of MDA production induced by Hyp was significantly reversed by IbTX in VSMCs. The study indicates that Hyp has the therapeutic potential to improve vascular outcomes, and the mechanism is associated with suppressing oxidative stress and improving CBF through upregulating BK channels.

Purpose: To explore the therapeutic efficiency of acupuncture and the related molecular mechanism of neural plasticity in depression.

Methods: Chronic unpredictable mild stress- (CUMS-) induced rats were established for the depression animal model. There were a total of four rat groups, including the control group, the CUMS group, the CUMS+acupuncture group, and the CUMS+fluoxetine group. The acupuncture group and the fluoxetine group were given a 3-week treatment after the modeling intervention. The researcher performed the open-field, elevated plus maze, and sucrose preference tests to evaluate depressive behaviors. The number of nerve cells, dendrites' length, and the prefrontal cortex's spine density were detected using Golgi staining. The prefrontal cortex expression, such as BDNF, PSD95, SYN, and PKMZ protein, was detected using the western blot and RT-PCR.

Results: Acupuncture could alleviate depressive-like behaviors and promote the recovery of the neural plasticity functions in the prefrontal cortex, showing the increasing cell numbers, prolonging the length of the dendrites, and enhancing the spine density. The neural plasticity-related proteins in the prefrontal cortex, including BDNF, PSD95, SYN, and PKMZ, were all downregulated in the CUMS-induced group; however, these effects could be partly reversed after being treated by acupuncture and fluoxetine (P < 0.05).

Conclusion: Acupuncture can ameliorate depressive-like behaviors by promoting the recovery of neural plasticity functions and neural plasticity-related protein upregulation in the prefrontal cortex of CUMS-induced depressed rats. Our study provides new insights into the antidepressant approach, and further studies are warranted to elucidate the mechanisms of acupuncture involved in depression treatment.

This study was aimed at investigating the functional connectivity (FC) changes between the insular subregions and whole brain in patients with obstructive sleep apnea (OSA) after 6 months of continuous positive airway pressure (CPAP) treatment and at exploring the relationship between resting-state FC changes and cognitive impairment in OSA patients. Data from 15 patients with OSA before and after 6 months of CPAP treatment were included in this study. The FC between the insular subregions and whole brain was compared between baseline and after 6 months of CPAP treatment in OSA. After 6 months of treatment, OSA patients had increased FC from the right ventral anterior insula to the bilateral superior frontal gyrus and bilateral middle frontal gyrus and increased FC from the left posterior insula to the left middle temporal gyrus and left inferior temporal gyrus. Hyperconnectivity was found from the right posterior insula to the right middle temporal gyrus, bilateral precuneus, and bilateral posterior cingulate cortex, which mainly involved the default mode network. There are changes in functional connectivity patterns between the insular subregions and whole brain in OSA patients after 6 months of CPAP treatment. These changes provide a better understanding of the neuroimaging mechanisms underlying the improvement in cognitive function and emotional impairment in OSA patients and can be used as potential biomarkers for clinical CPAP treatment.

While infant cues are often assumed to innately motivate maternal response, recent research highlights how the neural coding of infant cues is altered through maternal care. Infant vocalizations are important social signals for caregivers, and evidence from mice suggests that experience caring for mouse pups induces inhibitory plasticity in the auditory cortex (AC), though the molecular mediators for such AC plasticity during the initial pup experience are not well delineated. Here, we used the maternal mouse communication model to explore whether transcription in AC of a specific, inhibition-linked, memory-associated gene, brain-derived neurotrophic factor (Bdnf) changes due to the very first pup caring experience hearing vocalizations, while controlling for the systemic influence of the hormone estrogen. Ovariectomized and estradiol or blank-implanted virgin female mice hearing pup calls with pups present had significantly higher AC exon IV Bdnf mRNA compared to females without pups present, suggesting that the social context of vocalizations induces immediate molecular changes at the site of auditory cortical processing. E2 influenced the rate of maternal behavior but did not significantly affect Bdnf mRNA transcription in the AC. To our knowledge, this is the first time Bdnf has been associated with processing social vocalizations in the AC, and our results suggest that it is a potential molecular component responsible for enhancing future recognition of infant cues by contributing to AC plasticity.