Neuroscience
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Ambient temperature changes trigger plastic biological responses. Cold temperature is detected by the somatosensory system and evokes perception of cold together with adaptive physiological responses. We addressed whether chronic cold exposure induces adaptive adjustments of (1) thermosensory behaviours, and (2) the principle molecular cold sensor in the transduction machinery, transient receptor potential melastatin subtype 8 (TRPM8). ⋯ Furthermore, subcutaneous injection of the TRPM8 agonist icilin, enhanced cold avoidance in both groups in the Thermal Gradient Test, but Cold group mice were significantly less affected by icilin. Primary sensory neuron soma are located in dorsal root ganglia (DRGs), and western blotting showed diminished TRPM8 levels in DRGs of Cold group mice, as compared to the Thermoneutral group. We conclude that acclimation to chronic cold altered thermosensory behaviours, so that mice appeared less cold sensitive, and potentially, TRPM8 is involved.
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Circadian rhythms are regulated by a set of brain structures, one of which is the Intergeniculate Leaflet of the Thalamus (IGL). The most recognised role of the IGL is the integration of a variety of stimuli affecting rhythmicity, such as lighting conditions, received by the eye, or light-independent (non-photic) cues, the information about which is delivered via the activation of the non-specific projections. One of them is the norepinephrinergic system originating in the brainstem Locus Coeruleus (LC). ⋯ Using both agonists and antagonists of specific NE receptor subtypes, we confirmed the presence of functional α1-, α2- and β-adrenergic receptors within the investigated structure, allowing NE to exert multiple types of effects on different IGL neurons, mainly depolarisation of the neurons projecting to the Suprachiasmatic Nuclei - the master circadian pacemaker, and various responses exhibited by the cells creating the connection with the contralateral IGL. Moreover, NE was shown to affect IGL cells both directly and via modulation of the synaptic network, in particular the miniature inhibitory postsynaptic currents. To the best of our knowledge, these are the first studies to confirm the effects of NE on the activity of the IGL network.
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Review
The Roles of Oxidative Stress in Regulating Autophagy in Methylmercury-induced Neurotoxicity.
Methylmercury (MeHg) is a potential neurotoxin that is highly toxic to the human central nervous system. Although MeHg neurotoxicity has been widely studied, the mechanism of MeHg neurotoxicity has not yet been fully elucidated. Some research evidence suggests that oxidative stress and autophagy are important molecular mechanisms of MeHg-induced neurotoxicity. ⋯ The current study reviews the activation of Nuclear factor-erythroid-2-related factor (Nrf2)-related oxidative stress pathways and autophagy signaling pathways in the case of MeHg neurotoxicity. In addition, autophagy mainly plays a role in the neurotoxicity of MeHg through mTOR-dependent and mTOR-independent autophagy signaling pathways. Finally, the regulation of autophagy by reactive oxygen species (ROS) and Nrf2 in MeHg neurotoxicity was explored in this review, providing a new concept for the study of the neurotoxicity mechanism of MeHg.
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The transport mechanism of intestinal α-synuclein to the central nervous system has become a new hot topic in Parkinson's disease (PD) research. It is worth noting that the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been reported to be involved in the pathogenesis of PD. After silencing GAPDH expression by GAPDH siRNA, the normal human intestinal epithelial crypt-like (HIEC) and human SH-SY5Y neuroblastoma cell lines were co-cultured with Escherichia coli cells which were transfected with an α-synuclein overexpression plasmid. ⋯ Oxidative stress was assessed by measuring the levels of reactive oxygen species (ROS) using 2',7'-dichlorofluorescein diacetate (DCFH-DA), thiobarbituric acid-reactive substances (TBARS), and antioxidant capacity was assessed by measuring the glutathione (GSH) levels and superoxide dismutase (SOD) activity. The silencing of the expression of GAPDH pre-knockdown was found to reduce the intracellular levels of ROS and lipid peroxidation, enhance autophagy activity, thereby reducing the cell injury, apoptosis and necrosis induced by exogenous α-synuclein protein in SH-SY5Y cells. This study identifies a new therapeutic target of exogenous α-synuclein protein induced SH-SY5Y cell injury and improves our understanding of the pathophysiological role of GAPDH in vitro.
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α-Synuclein (α-syn), especially its abnormal oligomeric and phosphorylated form, plays a critical role in the pathogenesis of Parkinson's disease (PD). Plasma exosomal α-syn species have been shown to be a promising PD biomarker. However, whether different α-syn species in plasma exosomes (the oligomeric α-syn and the Ser129 phosphorylated α-syn (p-α-syn)) which represent the PD pathogenesis in the brain could be specific peripheral PD biomarker haven't been well elucidated. ⋯ Aggregated α-syn and p-α-syn existed both inside and on the membrane surface of plasma exosomes. The Receiver operating characteristic (ROC) performance of α-syn oligomer/total α-syn in exosomes was moderately helpful in PD diagnosis (AUC = 0.71, sensitivity = 60.5%, specificity = 59.4%), and the ratio of p-α-syn oligomer/total p-α-syn showed similar result (AUC = 0.69, sensitivity = 60.0%, specificity = 59.5%). This study indicates that the oligomeric α-syn/total α-syn and oligomeric p-α-syn/total p-α-syn ratio in plasma exosomes may be applied to assist the PD diagnosis, which needs further research.