Brain Research Bulletin最新文献

Cognitive dysfunction is one of the common comorbidities of epilepsy. More than 60% of epilepsy patients may experience impairment in learning, memory, attention, and executive control. At present, it can only control the symptoms of seizures, and there is no specific treatment for cognitive impairment. Deep brain stimulation (DBS) has been used to treat intractable epilepsy, with proven safety. Recently data suggests that DBS can not only improve the seizure control, but also improved cognitive function. This review summarizes the effects of DBS on cognitive impairment in epilepsy, including the current status and application of DBS, the influence of different DBS targets on brain of DBS on cognitive impairment in epilepsy, the possible mechanisms of DBS on cognitive impairment and its future prospects. It provides a theoretical basis for its further clinical application in epilepsy patients with cognitive dysfunction.

The exact mechanism underlies the development of neuropathic pain is not yet completely understood. Mitogen and stress-activated kinase 1 (MSK-1) is an important downstream kinase of the mitogen-activated protein kinase (MAPK). It has been extensively studied in the central nervous system, but whether MSK-1 is associated with the neuropathic pain remains elusive. In this experiment, Lumbar 5 spinal nerve ligation (SNL) was used to establish a neuropathic pain condition in the rats. Western blotting, qRT-PCR, immunohistochemistry, intrathecal catheterization and drugs delivery were evaluated to study the physiological responses of the animals. The results showed that SNL resulted in elevated phosphorylated MSK-1 (p-MSK-1) expression in the ipsilateral dorsal root ganglion (DRG) and the spinal dorsal horn in rats, while total MSK-1 (t-MSK-1) did not change significantly. Intrathecal injection of the MSK-1 inhibitor SB747651A partially reversed established neuropathic pain. Additionally, intrathecal administration of MSK-1 siRNA either preoperatively or 7 days postoperatively relieves the development and maintenance of pain, respectively. Meanwhile, the expression levels of p-H3S10, a downstream target of MSK-1, also displayed a significant increase after SNL. And these changes could be reversed by using MSK-1 siRNA. Collectively, the increase of MSK-1 induced by SNL participates in the development and maintenance of neuropathic pain by regulating the expression of p-H3S10 in DRG and spinal dorsal horn. Concentrating on MSK-1 may result in a novel approach to the treatment of neuropathic pain.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that place a huge economic and emotional burden on society. Salidroside (Sal) has been reported to have therapeutic effects in a variety of neurological disorders such as Alzheimer's disease （AD） and Parkinson's disease (PD), however no studies have been conducted to show whether salidroside is effective in ASD. Pyroptosis is involved in the pathology of a variety of neurological disorders, but has not been reported in ASD.

Objectives: The aim of this study was to investigate whether pyroptosis is involved in the pathological mechanisms of ASD, and whether salidroside has an impact on the pathological process of ASD by regulating pyroptosis.

Methods: We obtained a rat model of offspring ASD by prenatal intraperitoneal administration of valproic acid (VPA, 500mg/kg) to pregnant rats, and we treated seven-day-old offspring ASD with salidroside (Sal, 30mg/kg once daily) by gavage for 28 days as the salidroside treatment group. We examined the hippocampal state of ASD rats and the effect of salidroside on the hippocampus of VPA-induced ASD rats. In addition, in BV2 cells treated with LPS/Nig, we explored the mechanisms by which salidroside regulates neuroinflammation and pyroptosis in vitro.

Results: In vivo, we observed VPA-induced hippocampal neuronal damage and activation of the NLRP3/Caspase-1/GSDMD signalling pathway in ASD rats, while salidroside alleviated neuronal damage in ASD rats. In vitro, we found that salidroside inhibited LPS/Nig-induced neuroinflammation and activation of the NLRP3/Caspase-1/GSDMD signalling pathway. These results suggest that the therapeutic effect of salidroside on hippocampal damage in ASD rats may be related to NLRP3/Caspase-1/GSDMD-mediated pyroptosis.

Conclusions: Our work showed that salidroside ameliorates hippocampal neurological damage in ASD rats by targeting NLRP3/Caspase-1/GSDMD-mediated pyroptosis, providing a potential therapy drug for ASD.

Exercise can effectively prevent and treat depression and anxiety, with gut microbiota playing a crucial role in this process. Studies have shown that exercise can influence the diversity and composition of gut microbiota, which in turn affects depression through immune, endocrine, and neural pathways in the gut-brain axis. The effectiveness of exercise varies based on its type, intensity, and duration, largely due to the different changes in gut microbiota. This article summarizes the possible mechanisms by which exercise affects gut microbiota and how gut microbiota influences depression. Additionally, we reviewed literature on the effects of exercise on depression at different intensities, types, and durations to provide a reference for future exercise-based therapies for depression.

There is growing evidence that the imbalance of inflammatory cytokines plays an important role in the pathophysiological mechanism of depression. However, the effects of inflammatory cytokines on the whole brain in patients with depression are still not fully elucidated. The present study aimed to investigate the relationship between inflammatory cytokines and cerebral magnetic resonance imaging (MRI) features using voxel-based whole-brain analysis in patients with depression. A total of 60 patients with depression and 60 healthy controls (HCs) were included. Interleukin-1 was positively correlated with gray matter volume (GMV) in the left putamen and negatively correlated with regional homogeneity (ReHo) and degree centrality (DC) in the left anterior cingulate cortex. Interleukin-6 was positively correlated with GMV in the right superior parietal lobule and ReHo in the left pallidum and putamen. Interferon-α was negatively correlated with DC in the left postcentral gyrus. The ReHo in the left pallidum in depressed patients was lower than that in HCs. The FCs based on the left pallidum as the seed in depressed patients were significantly reduced. The imaging features of the left pallidum had good performance (area under the curve: 0.891) for identifying depressed patients. Inflammatory cytokines are associated with cerebral imaging features in patients with depression and in particular, the abnormal imaging features of the left pallidum may be a potential neuroimaging biomarker of depression.

The effectiveness of rehabilitation is contingent upon the motor recovery process which typically involves long-term motor skill re-acquisition. Given that the learning process can be modulated by task difficulty, elucidating the underlying neural mechanism is essential for optimizing rehabilitation prescription to suit different patient conditions. This study aimed to investigate the impact of task difficulty on cortical response during force-control training via electroencephalography (EEG). An 8-day visuomotor force-tracking training experiment was conducted. Healthy right-handed participants (N=33) were recruited and randomly assigned to 3 groups, and each group was tasked with a different level of difficulty. The task difficulty was manipulated by variation in force-production complexity and execution sequence assignments, with real-time visual feedback provided to participants for self-output adjustment. Behavioral performance was quantitatively assessed using a pre-defined score metric related to performance accuracy. The EEG signals were collected, and corresponding event-related desynchronization (ERD) and relative functional connectivity (FC) during the task execution were analyzed within the alpha- (8-13 Hz) and beta- (15-30 Hz) bands. A post-training experiment was also performed to evaluate the near-transfer capability of learning. Results showed all the behavioral performances improved during practice, while higher task difficulty level was affiliated with better post-training near-transfer ability. The dynamic neural response to training could be mediated by changes in difficulty level, where increased task complexity corresponded with the heightened activities in the beta-band priorly within the right dorsolateral prefrontal area. Additionally, stronger alpha-band functional connectivity was observed to be predominantly associated with the left motor area (LMA) during challenging tasks, and the intensification in connectivity persisted selectively post-training which appeared to be acritical factor for skill transfer performance improvement. These findings illustrated the dynamic neural mechanism through which task difficulty affects behavioral performance during long-term motor training with accurate force-control purpose. The selectively strengthened functional connectivity may contribute to facilitating new task execution after training interventions. Therefore, beneficial neural modulation can be expected to be feasible by well-designed task difficulty strategies for effective motor rehabilitation.