Gold Nanoparticles with Dexmedetomidine Regulate GSK-3β to Reduce Neurocognitive Effects in Anesthetized Rats

The aim of this study was to explore the neurocognitive effects of dexmedetomidine-loaded gold nanoparticles (AuNPs-dexmedetomidine) on anesthetized rats. Sixty Sprague Dawley rats (age, 2–3 weeks; weight, 250–280 g) were randomly divided into three groups (n = 20): the control group and two groups that received intraperitoneal injection of AuNPs-dexmedetomidine at 50 and 100 μg/kg each. Western blotting and RT-PCR were used to determine the protein and mRNA expression of GSK-3β, respectively. Compared with that in the control group, GSK-3β expression in AuNP-dexmedetomidine groups increased (P < 0.05). The protein expression of GSK-3β was higher and mRNA expression was significantly lower in the 100 μg/kg AuNP-dexmedetomidine group (P < 0.05). AuNPs-dexmedetomidine reduced the neurocognitive effect on anesthetized rats through the regulation of the GSK-3β signaling pathway.

First in human trial of a type I positive allosteric modulator of alpha7-nicotinic acetylcholine receptors: Pharmacokinetics, safety, and evidence for neurocognitive effect of AVL-3288

Type I positive allosteric modulators (PAMs) of the alpha7-nicotinic receptor enhance its cholinergic activation while preserving the spatiotemporal features of synaptic transmission and the receptor’s characteristic rapid desensitization kinetics. Alpha7-nicotinic receptor agonists have shown promise for improving cognition in schizophrenia, but longer-term trials have been disappointing. Therefore, the type I PAM AVL-3288 was evaluated for safety and preliminary evidence of neurocognitive effect in healthy human subjects. Single-dose oral administration in ascending doses was conducted in a double-blind, placebo-controlled Phase I trial in non-smokers. The trial found indication of positive but non-significant effects on neurocognition at 10 and 30 mg, two doses that produced overlapping peak levels. There was also some evidence for effects on inhibition of the P50 auditory evoked potential to repeated stimuli, a biomarker that responds to alpha7-nicotinic receptor activation. The pharmacokinetic characteristics were consistent between subjects, and there were no safety concerns. The effects and safety profile were also assessed at 3 mg in a cohort of smokers, in whom concurrent nicotine administration did not alter either effects or safety. The trial demonstrates that a type I PAM can be safely administered to humans and that it has potential positive neurocognitive effects in central nervous system (CNS) disorders.

An fMRI study of level of proficiency as a predictor of neurocognitive convergence for L1/L2 during a lexicosemantic task in a paediatric population

Studies on bilingualism from a neurocognitive perspective have begun to attract considerable interest recently. Contextual variables — such as age of acquisition, level of proficiency and frequency of use — have been identified as significantly impacting on the convergence or divergence of representations in first language (L1) and second (L2) language acquisition. The neurocognitive effect of bilingualism in paediatric populations, nevertheless, has not been widely investigated. Results from recent bilingual neuroimaging studies of word processing are discussed and compared to results obtained from a functional magnetic resonance imaging (fMRI) study of bilingual primary school children executing a productive lexicosemantic task. Previous studies indicate `level of proficiency' as a determinant of convergence of L1/L2 patterns during lexicosemantic tasks. Our results suggest that level of proficiency may be an inadequate predictor of convergence at least in paediatric populations, and demonstrate early influence of sequential bilingualism on the mother tongue as well.