Neurochemical Research最新文献

The central nervous system (CNS) comprises membranes and barriers that are vital to brain homeostasis. Membranes form a robust shield around neural structures, ensuring protection and structural integrity. At the same time, barriers selectively regulate the exchange of substances between blood and brain tissue, which is essential for maintaining homeostasis. Another highlight is the glymphatic system, which cleans metabolites and waste from the brain. Traumatic brain injury (TBI) represents a significant cause of disability and mortality worldwide, resulting from the application of direct mechanical force to the head that results in a primary injury. Therefore, this review aims to elucidate the mechanisms associated with the secondary injury cascade, in which there is intense activation of glial cells, dysfunction of the glymphatic system, glutamatergic neurotoxicity, additional molecular and biochemical changes that lead to a neuroinflammatory process, and oxidative stress and in which way they can be associated with cognitive damage that is capable of lasting for an extended period.

The ALG13 gene encodes a subunit of the uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) transferase enzyme, which plays a key role in the N-linked glycosylation pathway. This pathway involves the attachment of carbohydrate structures to asparagine (Asn) residues in proteins within the endoplasmic reticulum, by which N-glycosylated proteins produced participate a wide range of processes such as electrical gradients formation and neurotransmission. Mutations in the ALG13 gene have been identified as a causative factor for congenital disorders of glycosylation (CDG) and have been frequently associated with epilepsy in affected individuals. Several studies have demonstrated a strong correlation between abnormal N-glycosylation due to ALG13 deficiency and the onset of epilepsy. Despite these findings, the precise role of ALG13 in the pathogenesis of epilepsy remains unclear. This review provides a comprehensive overview of the current literature on ALG13-related disorders, with a focus on recent evidence regarding its role in epilepsy development and progression. Future research directions are also proposed to further elucidate the molecular mechanisms underlying this association.

Brain-derived neurotrophic factor (BDNF) is essential for the development and functioning of the vestibular system. BDNF promotes the growth, differentiation, and synaptic plasticity of vestibular neurons, ensuring their normal operation and maintenance. According to research, BDNF is pivotal during vestibular compensation, aiding in the recovery of neuron function by remodeling the spontaneous resting potentials of damaged vestibular neurons. Additionally, BDNF exhibits dose-dependent and age-dependent characteristics during vestibular system development, with its deficiencies leading to the degeneration of vestibular neurons. BDNF dynamically interacts with other neurotrophic factors, such as fibroblast growth factor-2 (FGF-2) and glial cell line-derived neurotrophic factor (GDNF), synergistically enhancing neuron survival and functionality. This review outline the function of BDNF in the vestibulocochlear system and explores its potential therapeutic applications, offering fresh perspectives and guidance for future research and treatment of vestibulocochlear system disorders.

Post-traumatic stress disorder (PTSD) poses significant neurological and psychiatric challenges. Investigations into the glutamatergic system, particularly the N-methyl-D-aspartate (NMDA) receptor, are crucial for understanding PTSD mechanisms. This study aimed to evaluate the therapeutic potential of the non-competitive NMDA receptor antagonist memantine in mitigating PTSD symptoms and to explore its underlying cellular and molecular impacts. Male Sprague Dawley rats were subjected to inescapable foot shock stress (FS-stress) to model PTSD. Following stress exposure, memantine was administered at doses of 5 mg/kg and 10 mg/kg six hours post-stress. Behavioural assessments, including fear conditioning and sucrose preference tests, were conducted. Golgi-Cox staining was used to assess neuroanatomical changes related to synaptic plasticity. Western blotting was used to analyse molecular markers associated with synaptic plasticity, while immunoassays measured proinflammatory cytokines and cortisol levels. Memantine treatment improved behavioral outcomes, restoring sucrose preference and reducing freezing behavior. Morphological analysis demonstrated that memantine enhanced dendritic spine structure, particularly increasing the proportion of mature mushroom spines, which are critical for synaptic stability. Additionally, memantine normalized cortisol levels, suggesting a regulatory effect on the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, memantine treatment improved the inflammatory cytokine profile, reducing IL-6 and TNF-α levels. These results suggest that memantine has potential as a therapeutic intervention for PTSD by targeting critical pathways involved in stress responses.The findings indicate that memantine, an NMDA receptor antagonist, can counteract behavioral and functional disturbances induced by FS-stress.

This study aimed to evaluate the cognitive-enhancing and neuroprotective effects of cardamonin in the 5XFAD transgenic mouse model of Alzheimer’s disease (AD). We treated six-month-old female 5XFAD mice with cardamonin at 5 mg/kg, 10 mg/kg, and 20 mg/kg. Cognitive function was assessed using the Morris Water Maze (MWM) and Novel Object Recognition (NOR) tests. ELISA, western blot, and PCR analyses evaluated amyloid-beta (Aβ) levels, neuroinflammation markers, and apoptosis-related factor expression. All animals survived without toxicity. Cardamonin treatment significantly improved spatial learning and memory retention in MWM and NOR tests, with the 20 mg/kg dose showing the most pronounced effects. Additionally, cardamonin reduced soluble and insoluble Aβ levels in the frontal cortex and hippocampus. The treatment also significantly decreased neuroinflammatory markers, with IL-1β, IL-6, and TNF-α levels dropping substantially at higher doses. Cardamom treatment also normalizes cleaved caspase 3, GFAP, Iba-1, PSD-95, and synaptophysin, which aids in restoring synaptic integrity. Furthermore, cardamonin led to a marked reduction in apoptosis-related gene expression, indicating its potential to mitigate neurodegeneration. Cardamonin demonstrates significant cognitive-enhancing and neuroprotective properties in the 5XFAD mouse model, suggesting its potential as a therapeutic agent for AD. These findings support further investigation into cardamonin’s mechanisms and applicability in treating neurodegenerative disorders.

Mitochondrial dysfunction is well recognized as a critical component of the complicated pathogenesis of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. This review investigates the influence of mitochondrial DNA single nucleotide polymorphisms on mitochondrial function, as well as their role in the onset and progression of these neurodegenerative diseases. Furthermore, the contemporary approaches to mitochondrial regulation in these disorders are discussed. Our objective is to uncover early diagnostic targets and formulate precision medicine strategies for neurodegenerative diseases, thereby offering new paths for preventing and treating these conditions.

Among the spectrum of gliomas, glioblastoma stands out as the most aggressive brain tumor affecting the central nervous system. In addressing this urgent medical challenge, exploring therapeutic alternatives becomes imperative to enhance the patient’s prognosis. In this regard, Butia odorata (BO) fruit emerges as a promising candidate due to its array of bioactive compounds, including flavonoids, phenolic acids, and carotenoids, known for their antioxidant, anti-inflammatory, and antitumor properties. Thus, this study aimed to investigate the impact of standardized hydroalcoholic extract of BO on rat C6 and human U87MG glioma cell lines. Cells were exposed to varying extract concentrations (125–2000 μg/mL) for intervals of 0, 2, 4, 6, 24, 48, or 72 h. Then, cell viability, proliferation, colony formation, redox equilibrium parameters, cell migration, and the relative mRNA expression of genes related to gliomagenesis were evaluated. Our findings revealed a reduction in viability, proliferation, colony formation, reactive oxygen species, and nitrite levels in both glioma cell lines upon exposure to the extract. Conversely, an increase in sulfhydryl content and the activity of superoxide dismutase and catalase were observed in both glioma cell lines. No significant changes in viability and proliferation were observed in astrocytes. Furthermore, in the C6 cells only, the BO extract reduced the migration and downregulated the relative mRNA expression of matrix metalloproteinase-2, O6-methylguanine-DNA methyltransferase, nuclear factor-kappa B, interleukin-6 genes, and upregulated caspase-3 gene. These results underscore the promising anti-glioma potential of BO extract, attributed to its diverse bioactive composition.

A sharp increase in intramedullary pressure after spinal cord injury (SCI) can aggravate secondary injury and lead to severe neurological deficits. Unfortunately, effective treatment options are currently lacking. The mechanosensitive ion channel Piezo1 plays an important role in the pathological process of SCI by transducing mechanical stress. The Piezo1 inhibitor GsMTx4 has been shown to have neuroprotective effects and may hold therapeutic potential for SCI. Given that single drug treatment strategy has limited effect on functional recovery after SCI, we explored the efficacy of combining GsMTx4 with exercise training in treating SCI in rats and investigated the underlying mechanisms. We used the T10 SCI rat model, administered GsMTx4 immediately after injury, and performed 4 weeks of body weight supported treadmill training starting (BWSTT) 2 weeks post injury. Subsequently, HE and LFB staining were used to observe the morphology of spinal cord tissue, WB was used to detect autophagy and apoptosis-related proteins, biochemical detection of calcium ion concentration and CTSD activity, IHC detection of LAMP1 expression, immunofluorescence labeling of NeuN and ChAT-positive motor neurons, as well as MBP and GFAP, and BBB scores were used to evaluate rat motor function. We found that the combined treatment of GsMTx4 drug and exercise training was more effective than single treatment alone. The combined treatment reduced calcium ion concentration, improved lysosomal function, enhanced autophagic flux, reduced cell apoptosis, and significantly improved the motor function of rats. This combined treatment regimen may pave the way for developing more comprehensive treatment strategies for SCI in the future.

Graphical Abstract

Mechanism diagram. Piezo1 inhibitors combined with exercise exerts neuroprotective effects by regulating neuronal autophagy. Excessive mechanical stress following spinal cord injury (SCI) over activates the mechanosensitive Piezo1 channel in spinal neurons, leading to increased Ca²⁺ release and subsequent lysosomal dysfunction. This dysfunction decreases autophagic flux, potentially resulting in neuronal apoptosis, exacerbated glial scar formation, and demyelination. The application of Piezo1 inhibitors improves lysosomal function and enhances autophagic flux, thereby reducing cell apoptosis. Additionally, exercise training further amplifies the neuroprotective effects of Piezo1 inhibitors, contributing to overall neuronal recovery.