Vogelyildirim7109

Furthermore, the anti-nociceptive effect of EMD-386088 on neuropathic pain was prevented by the adenylate cyclase (AC) inhibitor SQ-22536, and protein kinase A (PKA) inhibitor H89, suggesting that AC/PKA signaling might underlie the antinociception of agonists. Finally, the 5-HT6 receptors were found to be colocalized with a glutamate transporter (EAAC1) by immunofluorescent staining, and the glutamate receptor antagonist kynurenic acid was found to completely block antinociception. These findings indicated that the antinociceptive effect of 5-HT6 receptor agonists might occur via interaction with the glutamatergic system. Altogether, the agonists activated 5-HT6 receptors present in the glutamatergic neurons in the VLO to facilitate the AC/PKA cascade, which subsequently might evoke glutamate release, thus depressing allodynia. These findings suggest a potential therapeutic role of 5-HT6 receptor agonists in treating neuropathic pain.Sleep disturbances have been recognized as a core symptom of post-traumatic stress disorders (PTSD). However, the neural basis of PTSD-related sleep disturbances remains unclear. It has been challenging to establish the causality link between a specific brain region and traumatic stress-induced sleep abnormalities. Here, we found that single prolonged stress (SPS) could induce acute changes in sleep/wake duration as well as short- and long-term electroencephalogram (EEG) alterations in the isogenic mouse model. Moreover, the medial prefrontal cortex (mPFC) showed persistent high number of c-fos expressing neurons, of which more than 95% are excitatory neurons, during and immediately after SPS. Chemogenetic inhibition of the prelimbic region of mPFC during SPS could specifically reverse the SPS-induced acute suppression of delta power (1-4 Hz EEG) of non-rapid-eye-movement sleep (NREMS) as well as most of long-term EEG abnormalities. These findings suggest a causality link between hyper-activation of mPFC neurons and traumatic stress-induced specific sleep-wake EEG disturbances.

To evaluate whether introducing gamification in BCI rehabilitation of the upper limbs of post-stroke patients has a positive impact on their experience without altering their efficacy in creating motor mental images (MI).

A game was designed purposely adapted to the pace and goals of an established BCI-rehabilitation protocol. Rehabilitation was based on a double feedback functional electrostimulation and animation of a virtual avatar of the patient's limbs. The game introduced a narrative on top of this visual feedback with an external goal to achieve (protecting bits of cheese from a rat character). A pilot study was performed with 10 patients and a control group of six volunteers. Two rehabilitation sessions were done, each made up of one stage of calibration and two training stages, some stages with the game and others without. The accuracy of the classification computed was taken as a measure to compare the efficacy of MI. Users' opinions were gathered through a questionnaire.



The gamified rehabilitation presented in the pilot study does not impact on the efficacy of MI, but it improves users experience making it more fun.

These preliminary results are encouraging to continue investigating how game narratives can be introduced in BCI rehabilitation to make it more gratifying and engaging.

These preliminary results are encouraging to continue investigating how game narratives can be introduced in BCI rehabilitation to make it more gratifying and engaging.Inhalants, including volatile organic solvents such as toluene, continue to be one of the most prevalent, and often first substances abused by adolescents. Bestatin research buy Like other drugs of abuse, toluene affects the function of neurons within key brain reward circuits including the prefrontal cortex, ventral tegmental area, and nucleus accumbens. However, preclinical models used to study these toluene-induced adaptations generally employ passive exposure paradigms that do not mirror voluntary patterns of solvent exposure observed in humans. To address this shortcoming, we developed an inhalation chamber containing active and inactive nose pokes, cue lights, flow-through vaporizers, and software-controlled valves to test the hypothesis that rats will voluntarily self-administer toluene vapor. Following habituation and self-administration (SA) training rats achieve vapor concentrations associated with rewarding effects of toluene, and maintain responding for toluene vapor, but not for air. During extinction trials, rats showed an initial burst of drug-seeking behavior similar to that of other addictive drugs and then reduced responding to Air SA levels. Responding on the active nose poke recovered during cue-induced reinstatement but not following a single passive exposure to toluene vapor. The results from these studies establish a viable toluene SA protocol that will be useful in assessing toluene-induced changes in addiction neurocircuitry.Nematode parasitosis causes significant mortality and morbidity in humans and considerable losses in livestock and domestic animals. The acquisition of resistance to current anthelmintic drugs has prompted the search for new compounds for which the free-living nematode Caenorhabditis elegans has emerged as a valuable platform. We have previously synthetized a small library of oxygenated tricyclic compounds and determined that dibenzo[b,e]oxepin-11(6H)-one (doxepinone) inhibits C. elegans motility. Because doxepinone shows potential anthelmintic activity, we explored its behavioral effects and deciphered its target site and mechanism of action on C. elegans. Doxepinone reduces swimming rate, induces paralysis, and decreases the rate of pharyngeal pumping required for feeding, indicating a marked anthelmintic activity. To identify the main drug targets, we performed an in vivo screening of selected strains carrying mutations in Cys-loop receptors involved in worm locomotion for determining resistance to doxepinone effects. A mutant strain that lacks subunit genes of the invertebrate glutamate-gated chloride channels (GluCl), which are targets of the widely used antiparasitic ivermectin (IVM), is resistant to doxepinone effects. To unravel the molecular mechanism, we measured whole-cell currents from GluClα1/β receptors expressed in mammalian cells. Glutamate elicits macroscopic currents whereas no responses are elicited by doxepinone, indicating that it is not an agonist of GluCls. Preincubation of the cell with doxepinone produces a statistically significant decrease of the decay time constant and net charge of glutamate-elicited currents, indicating that it inhibits GluCls, which contrasts to IVM molecular actions. Thus, we identify doxepinone as an attractive scaffold with promising anthelmintic activity and propose the inhibition of GluCls as a potential anthelmintic mechanism of action.