Neuroscience
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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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Burst suppression (BS) is an electroencephalogram (EEG) pattern in which signals alternates between high-amplitude slow waves (burst waves) and nearly flat low-amplitude waves (suppression waves). In this study, we used wide-field (8.32 mm × 8.32 mm) fluorescent calcium imaging to record the activity of glutamatergic neurons in the parietal and occipital cortex, in conjunction with EEG recordings under BS induced by different anesthetics (sevoflurane, isoflurane, and propofol), to investigate the spatiotemporal pattern of neural activity under BS. The calcium signal of all observed cortices was decreased during the phase of EEG suppression. ⋯ Correlation analysis showed a strong correlation between the EEG signal and the calcium signal in the medial cortex under BS (except for propofol induced signals). As the burst-suppression ratio (BSR) increased, the regions with strong correlation coefficients became smaller, but strong correlation coefficients were still noted in the medial cortex. Taken together, our results reveal the landscape of cortical activity underlying BS.
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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 progression of neurodegenerative disorders is mainly characterized by immense neuron loss and death of glial cells. The mechanisms which are active and regulate neuronal cell death are namely necrosis, necroptosis, autophagy and apoptosis. These death paradigms are governed by a set of molecular determinants that are pivotal in their performance and also exhibit remarkable overlapping functional pathways. ⋯ In addition, the review also focuses on the exorbitant number of newer molecules with the potential to cross communicate between death pathways and create a complex cell death scenario. This review highlights recent studies on the inter-dependent regulation of cell death paradigms in neurodegeneration, mediated by cross-communication between pathways. This will help in identifying potential targets for therapeutic intervention in neurodegenerative diseases.
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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.