Neuroscience
-
Reaching movements are essential for daily tasks and they have been widely investigated through kinematic, kinetic, and electromyographic (EMG) analyses. Recent studies have suggested that the central nervous system simplifies control of reaching movements by using muscle synergies. An alternative approach is to investigate how EMG activity reflects at theneural level with the representation of spinal maps that visualize the spatiotemporal activity of motoneuronal pools. ⋯ The multidimensional Pearson's correlation coefficient was used to assess thesimilarity of spinal maps among repetitions of movements within subjects (intra-subject variability) and among participants (inter-subject variability). Spinal maps of tonic and total EMG showed high intra- and inter-subject similarity in all planes, while phasic spinal maps were less repeatable and more subject-specific. These results may be useful as areference for rehabilitation, clinical, and neurological evaluations, especially for longitudinal assessments.
-
Epilepsy is a pathophysiological condition displaying a highly diverse phenotype. Consequently, comprehending the mechanisms underlying seizures necessitates moving beyond a simplistic model focused on the imbalance between the classical excitatory and inhibitory neurotransmitter systems. Nitric oxide (NO), a nonclassical and multifunctional gaseous neurotransmitter, has the potential to exert a profound influence on epileptic reactivity. ⋯ Notably, our research suggests that the level of NO synthesis does not interfere with the severity of the epileptic seizures that occur. In light of this, we propose that the nitrergic system is quickly activated in the epileptic brain as a compensatory mechanism of the central nervous system. However, under usual conditions, this activation is insufficient to effectively attenuate seizures.
-
Transparency of Caenorhabditis elegans enables microscopic in vivo imaging of cellular processes, but immobilization is required due to high locomotor activity. Here, anesthetic-like effects of dissociate anesthetic ketamine in adult C. elegans are presented using video recordings and infrared-based automated activity tracking. Ketamine caused a reversible blockade of locomotion at a similar concentration (20-50 mM) at which conventionally used immobilizing agent sodium azide (NaN3) produces paralysis. ⋯ However, a marked chemosensation deficiency was noted immediately after 20 mM ketamine exposure. Short-term ketamine treatment did not show signs of SKN-1 (skinhead-1) activation, a marker of the stress response associated with NaN3. In sum, our results show ketamine's potential as a non-toxic nematode immobilizing agent and rationalize C. elegans as a model organism to understand its pharmacology.
-
Intestinal immunity is associated with several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes. Recent evidence also suggests its implication in the pathogenesis of autoimmune diseases affecting the central nervous system, such as multiple sclerosis (MS). However, there is ongoing debate regarding which part of the intestinal tract contributes to the development of MS. ⋯ Additionally, we highlighted an increase in dendritic cells and monocytes/macrophages in the colonic lamina propria of EAE animals during the presymptomatic phase. Altogether, our findings indicate that both small intestine and colon are involved in the pathogenesis of EAE, despite engaging distinct immunological processes. This study provides new insights for understanding the roles of intestinal lymphoid and myeloid immune cells on the pathogenesis of MS and other autoimmune diseases.
-
Previously, we reported that both S-nitrosoglutathione (GSNO), a carrier of cellular nitric oxide, and N6022, an injectable form of GSNO reductase (GSNOR) inhibitor that increases endogenous GSNO levels, alleviate experimental autoimmune encephalomyelitis (EAE) in mice by suppressing Th1 and Th17 immune responses. Building on these findings, we explored the role of GSNOR in EAE pathogenesis and evaluated the efficacy of an orally active GSNOR inhibitor (N91115) in treating the EAE disease. EAE mice exhibited heightened expression/activity of GSNOR in the spinal cord, and the knockout of the GSNOR gene resulted in much milder clinical manifestations of EAE, with lower degrees of demyelination and axonal loss, reduced microglial and astrocyte activations, as well as suppressed Th1 and Th17 cell responses, alongside bolstered Treg immune responses. ⋯ This observation underscores the potential of increased GSNOR expression and activity as a risk factor exacerbating EAE immunopathology, while simultaneously highlighting its potential as a target for modifying the disease. Furthermore, the balanced immune regulation provided by orally active N91115 (IL-6/IL-17a vs. IL-10) presents a promising alternative to immunosuppressive drugs, reducing the risk of opportunistic infections.