Neuroscience
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To evaluate physiological roles of the large, second cytoplasmic loops (C2) situated between the M3 and M4 transmembrane domains of nicotinic acetylcholine receptor (nAChR) subunits. We have constructed chimeric β2 (β2χ) and β4 (β4χ) subunits in which the "nested" C2 domains (but not the "proximal" sequences of ∼14 residues immediately adjacent to the M3 or M4 domains) of these β subunits were replaced by the corresponding sequence from the serotonin 5-HT3A receptor subunit. We previously reported that heterologously expressed nAChR containing α4 and β2χ subunits displayed a faster whole-cell current decay in its agonist response compared to responses of all-wild-type α4β2-nAChR. ⋯ In addition, cell-attached, single-channel recording shows that both acetylcholine-activated α4β2χ- and α4β4χ-nAChR have a significantly lower mean open probability, shorter mean open-time, and a longer mean closed-time than their fully wild-type counterparts while not having different conductance amplitudes. These findings reveal microscopic bases for the faster desensitization of α4(∗)-nAChR containing chimeric instead of wild-type β subunits. Our findings also remain consistent with novel and unexpected roles of β subunit-nested C2 domains in modulation of α4(∗)-nAChR function.
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Tastes and odors influence the perception of a meal. Especially food aromas can act as potent signals to modulate our eating behavior with strong dependency on the reward produced by food. In this investigation we aimed to study the electrophysiological response to food- and non-food-related odors in healthy volunteers. Analyses revealed specific scalp potential maps for the two conditions; in particular the source of the map in the "food" condition seemed to be associated with the processing of rewards; the specific map in the "non-food" condition reflects odor characteristics excluding the reward.
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It has been documented that infection of herpes simplex virus type 1 (HSV-1) contributes to the initiation of Bell's palsy. However, the exact mechanisms responsible for this disorder have not been fully elucidated to date. A mouse model of facial palsy induced by HSV-1 provides an opportunity to investigate the alteration in activities of nuclear factor-kappa B (NF-κB) and its consequent effect on two key inflammatory factors, i.e., tumor necrosis factor (TNF)-α and cyclooxygenase-2 (COX-2), as well as the effect of glucocorticoids (GCs) in this work. ⋯ In addition, GCs inhibited the nuclear translocation and DNA binding activity of NF-κB via inhibiting IκB-α degradation. Meanwhile, TNF-α production and COX-2 expression were significantly reduced by GCs. In conclusion, HSV-1 inoculation induced the activation of NF-κB, expression and secretion of TNF-α and COX-2 in the facial paralyzed mice, while, glucocorticoid effectively down-regulated TNF-α and COX-2 expression in HSV-1-induced paralyzed mice.
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Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection that might cause permanent neurological deficits. Cannabidiol (CBD) is a nonpsychotomimetic compound of Cannabis sativa with neuroprotective properties. In the present work, we evaluated the effects of CBD in a murine model of CM. ⋯ On 5dpi, TNF-α and IL-6 increased in the hippocampus, while only IL-6 increased in the prefrontal cortex. CBD treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus (TNF-α) and prefrontal cortex (IL-6). Our results indicate that CBD exhibits neuroprotective effects in CM model and might be useful as an adjunctive therapy to prevent neurological symptoms following this disease.
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Altered expression of neuronal cytoskeletal proteins are known to play an important role in hyper-excitability of neurons in patients and animal models of epilepsy. Our previous work showed that cell division cycle 42 GTP-binding protein (Cdc42), a small GTPase of the Rho-subfamily, is significantly increased in the brain tissue of patients with temporal lobe epilepsy (TLE) and in the brain tissues of the epileptic model of rats. However, whether inhibition of Cdc42 can modify epileptic seizures has not been investigated. ⋯ Whole-cell patch-clamp recording on CA1 pyramidal neurons in hippocampal slices from pilocarpine-induced epileptic model demonstrated that ML141 significantly inhibits the frequency of action potentials (APs), increases the amplitude and frequency of miniature inhibitory postsynaptic currents (mIPSCs), and increases the amplitude of evoked inhibitory postsynaptic currents (eIPSCs). However, ML141 did not have an impact on the miniature excitatory postsynaptic currents (mEPSCs). Our results are the first to indicate that Cdc42 plays an important role in the onset and progression of epileptic-seizures by regulating synaptic inhibition.