Neuroscience
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Identified 40 years ago, the metabotropic glutamate (mGlu) receptors play key roles in modulating many synapses in the brain, and are still considered as important drug targets to treat various brain diseases. Eight genes encoding mGlu subunits have been identified. They code for complex receptors composed of a large extracellular domain where glutamate binds, connected to a G protein activating membrane domain. ⋯ The present review summarizes the approaches used to study their activation process and their pharmacological properties and to demonstrate their existence in vivo. We will highlight how the existence of mGlu heterodimers revolutionizes the mGlu receptor field, opening new possibilities for therapeutic intervention for brain diseases. As illustrated by the number of possible mGlu heterodimers, this study will highlight the need for further research to fully understand their role in physiological and pathological conditions, and to develop more specific therapeutic tools.
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Recent evidence has supported a pathogenic role for neuroinflammation in Parkinson's disease (PD). Inflammatory response has been associated with symptoms and subtypes of PD. However, it is unclear whether immune changes are involved in the initial pathogenesis of PD, leading to the non-motor symptoms (NMS) observed in its prodromal stage. ⋯ The striatum showed increased IL-17A, BDNF, and NFG levels compared to control mice. In conclusion, neuroinflammation may play an important role in the early stage of experimental PD-like syndrome, leading to cognitive and behavioral changes. Our results also indicate that intranasal administration of MPTP may represent a valuable mouse model for prodromal PD.
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Energy metabolism in the brain has been considered one of the critical research areas of neuroscience for ages. One of the most vital parts of brain metabolism cascades is lipid metabolism, and fatty acid plays a crucial role in this process. The fatty acid breakdown process in mitochondria undergoes through a conserved pathway known as β-oxidation where acetyl-CoA and shorter fatty acid chains are produced along with a significant amount of energy molecule. ⋯ Lipid droplet biology in peripheral organs like the liver and heart has been well investigated, while the brain's LDs have received less attention. Recently, there has been increased awareness of the existence and role of these dynamic organelles in the central nervous system, mainly connected to neurodegeneration. In this review, we discussed the role of beta-oxidation and lipid droplet formation in the oxidative phosphorylation process, which directly affects neurodegeneration through various pathways.
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Accurate movements of the upper limb require the integration of various forms of sensory feedback (e.g., visual and postural information). The influence of these different sensory modalities on reaching movements has been largely studied by assessing endpoint errors after selectively perturbing sensory estimates of hand location. These studies have demonstrated that both vision and proprioception make key contributions in determining the reach endpoint. ⋯ We trained subjects using a velocity-dependent force-field to probe the extent arm posture-dependent influences persisted after exposure to a motion-state dependent perturbation. Changes in the temporal force profiles due to variations in arm posture were not reduced by adaptation to novel movement dynamics, but persisted throughout learning. These results suggest that vision and posture differentially influence the internal estimation of limb state throughout movement and play distinct roles in forming the response to external perturbations during movement.
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Postoperative stroke is a challenging and potentially devastating complication after elective carotid endarterectomy (CEA). We previously demonstrated that transmembrane protein 166 (TMEM166) levels were directly related to neuronal damage after cerebral ischemia-reperfusion injury in rats. In this subsequent clinical study, we aimed to evaluate the prognostic value of TMEM166 in patients suffering from post-CEA strokes. ⋯ Furthermore, circulating TMEM166 concentrations were statistically higher in post-CEA stroke patients than in patients allocated to the control group. Mean plasma concentrations of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also elevated in patients with postoperative strokes. Therefore, based on these findings, we hypothesize that elevated TMEM166 levels, accompanied by a strong inflammatory response, serve as a useful biomarker for risk assessment of postoperative stroke following CEA.