Neurochemistry international
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Sulfuretin, a potent anti-oxidant, has been thought to provide health benefits by decreasing the risk of oxidative stress-related diseases. In this study, we investigated the mechanisms of sulfuretin protection of neuronal cells from cell death induced by the Parkinson's disease (PD)-related neurotoxin 6-hydroxydopamine (6-OHDA). We examined whether sulfuretin acts as an anti-oxidant to reduce oxidative stress and mitochondrial-mediated apoptotic cascade events in 6-OHDA-induced neurotoxicity in SH-SY5Y cells. ⋯ Eventually, sulfuretin inhibited 6-OHDA-induced NF-κB translocation to the nucleus induced by 6-OHDA. The results of the current study provide the first evidence that sulfuretin protects SH-SY5Y cells against 6-OHDA-induced neuronal cell death, possibly through inhibition of phosphorylation of MAPK, PI3K/Akt, and GSK-3β, which leads to mitochondrial protection, NF-κB modulations and subsequent suppression of apoptosis via ROS-dependent pathways. Thus, we conclude that sulfuretin may have a potential role for neuroprotection and, therefore, may be used as a therapeutic agent for PD.
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Fast synaptic inhibition in the adult brain is largely mediated by GABAA receptors (GABAAR). GABAAR are anchored to synaptic sites by gephyrin, a scaffolding protein that appears to be assembled as a hexagonal lattice beneath the plasma membrane. Brain derived neurotrophic factor (BDNF) alters the clustering and synaptic distribution of GABAAR but mechanisms behind this regulation are just starting to emerge. ⋯ Exogenous application of BDNF to immature neuronal cultures from rat hippocampus increased the protein levels and clustering of gephyrin. BDNF also augmented the association of gephyrin with GABAAR and promoted the formation of GABAAR clusters. Together, these observations indicate that BDNF might regulate the assembly of GABAergic synapses by promoting the association of GABAAR with gephyrin.
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Brain abscesses often cause symptoms of brain dysfunction, including seizures, suggesting interference with normal neurotransmission. We determined the concentration of extracellular neuroactive amino acids in brain abscesses from 16 human patients. Glutamate was present at 3.6 mmol/L (median value, range 0.5-10.8), aspartate at 1.0 mmol/L (range 0.09-6.8). ⋯ The patient groups did not differ with respect to abscess volume, the cerebral lobe affected, age, or time from symptom onset to surgery. Seven patients with extracerebral, intracranial abscesses had significantly lower pus concentration of glutamate (352 μmol/L, range 83-1368) and aspartate (71 μmol/L, range 22-330) than intracerebral abscesses (p<0.001). We conclude that excitatory amino acids glutamate and aspartate may reach very high concentrations in brain abscesses, probably contributing to symptoms through activation of glutamate receptors in the surrounding brain tissue.
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Zellweger syndrome (ZS) is a neonatal-lethal genetic disease that affects all tissues, and features neuropathology that involves primary developmental defects as well as neurodegeneration. Neuropathological changes include abnormal neuronal migration affecting the cerebral hemispheres, cerebellum and inferior olivary complex, abnormal Purkinje cell arborisation, demyelination and post-developmental neuronal degeneration. ⋯ Attempts to explain the neuropathogenesis have implicated peroxisomal metabolic dysfunction, and more specifically the loss of peroxisomal products, such as plasmalogens and docosahexaenoic, and the accumulation of peroxisomal substrates, such as very-long-chain-fatty acids. In this review, consideration is also given to recent findings that implicate other candidate pathogenetic factors, such as mitochondrial dysfunction, oxidative stress, protein misfolding, aberrant cell signalling, and inflammation - factors that have also been identified as important in the pathogenesis of other neurological diseases.
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Atorvastatin is an HMG-CoA reductase inhibitor used in the treatment of hypercholesterolemia and prevention of coronary heart disease. Oxidative stress is considered to be one of the main causes of neuropathic pain after nerve injury. This study aimed to investigate the effect of atorvastatin on oxidative stress and hyperalgesia in chronic constriction injury (CCI) model of neuropathic pain. ⋯ The levels of MDA, O2(-), and protein carbonyl in these tissues were significantly reduced in the atorvastatin-treated CCI rats compared to the untreated CCI rats. Our study demonstrated that atorvastatin attenuates neuropathic pain through inhibition of oxidative stress in sciatic nerve, spinal cord and brain suggesting antioxidants as potential drugs in neuropathic pain management. This study provides a new application of atorvastatin in treatment of neuropathic pain.