Neuroscience
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Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a fatal motoneuron disorder in children with unknown etiology. The disease is caused by mutations in the IGHMBP2 gene, encoding a Super Family 1 (SF1)-type RNA/DNA helicase. IGHMBP2 is a cytosolic protein that binds to ribosomes and polysomes, suggesting a role in mRNA metabolism. ⋯ Fluorescence Recovery after Photobleaching (FRAP) studies revealed translational down-regulation of an eGFP-myr-β-actin 3'UTR mRNA in growth cones. Local translational regulation of β-actin mRNA was dependent on the 3' UTR but independent of direct Ighmbp2-binding to β-actin mRNA. Taken together, our data indicate that Ighmbp2 deficiency results in local but modest disruption of protein biosynthesis which might partially contribute to the motoneuron defects seen in SMARD1.
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P2X2 receptors are ligand-gated cation channels activated by extracellular ATP that modulate neural transmission in various neuronal systems. Although the function and distribution of P2X2 receptors in the cochlea portion of the inner ear are well established, their physiological role in the vestibular portion is still not understood. Therefore, we investigated P2X2 receptor localization in the peripheral vestibular portion, and assessed their physiological function in vivo using P2X2 receptor knock out (P2X2-KO) mice. ⋯ VOR gain in P2X2-KO mice was significantly reduced, with no decrease in the optokinetic response. In conclusion, we showed that P2X2 receptors are mainly localized in the supporting cells of the vestibular inner ear, and the loss of P2X2 receptors causes mild vestibular dysfunction. Taken together, our findings suggest that the P2X2 receptor plays a modulatory role in vestibular function.
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Action observation is known to enhance sensorimotor system activation, and such effect has been linked to neural priming and response facilitation mechanisms. This facilitation effect, however, has been primarily studied by focusing on high-level motor proficiency, whereas evidence on the effect of observing poorly performed actions is still lacking. We then devised a study to investigate neural correlates of the observation of suboptimal motor acts as mirrored by corticospinal activation (via transcranial magnetic stimulation (TMS), Experiment 1) and by modulation of cortical oscillatory activity (via electroencephalography (EEG), Experiment 2). 40 participants were presented with four randomly reiterated videos. ⋯ Analyses highlighted both increased corticospinal excitability and desynchronized alpha-beta oscillations during the observation of poorly performed motor acts performed by the mildly impaired MS patient. Further, we observed gradually increasing beta activity across videos reiterations, specifically for the minimally impaired patient's video. Reported findings corroborate the hypotheses that the action-observation network and the motor system might be involved in processes evoked in the attempt to understand and predict observed actions which do not belong to the onlookers' motor repertoire, reflecting in an increased sensorimotor activity.
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Cholinergic stimulation coupled with visual conditioning enhances the visual acuity and cortical responses in the primary visual cortex. To determine which cholinergic receptors are involved in these processes, qRT-PCR was used. Two modes of cholinergic enhancement were tested: a phasic increase of acetylcholine release by an electrical stimulation of the basal forebrain cholinergic nucleus projecting to the visual cortex, or a tonic pharmacological potentiation of the cholinergic transmission by the acetylcholine esterase inhibitor, donepezil. ⋯ A Kruskal-Wallis test showed a modulation of the expression in the visual cortex of m2, m3, m4, m5, α7, β4, NMDA and GAD65, but only β4 within the basal forebrain and none of these mRNA within the somatosensory cortex. The two modes of cholinergic enhancement induced different effects on mRNA expression, related to the number of visual conditioning sessions and receptor specificity. This study suggests that the combination of cholinergic enhancement and visual conditioning is specific to the visual cortex and varies between phasic or tonic manipulation of acetylcholine levels.
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We previously demonstrated that the non-steroidal anti-inflammatory agent meloxicam has neuroprotective effects in an oxygen and glucose deprivation model (OGD) of rat organotypic hippocampal slice cultures. We wondered if GABAergic transmission changed the neuroprotective effects of meloxicam and if meloxicam was able to modulate endoplasmic reticulum stress (ER stress) in this model. Mortality was measured using propidium iodide. ⋯ However, in light of its effects on caspase 3 and PARP, bicuculline did not seem to promote the apoptotic pathway. Our results also showed that meloxicam modified the unfolded protein response (UPR), as well as the transcriptional response of different genes, including the GABAA receptor, alpha1, beta3 and gamma2 subunits. We concluded that meloxicam has a neuroprotective anti-apoptotic action, is able to enhance the UPR independently of the systemic anti-inflammatory response and its neuroprotective effect can be inhibited by blocking GABAA receptors.