Socio-economic status, executive functions, and theory of mind ability in adolescents: Relationships with language ability and cortisol.

Socio-economic status (SES) is linked to the development of cognitive abilities, particularly language and executive processes. It is unclear whether these represent a single or independent correlates. We studied 110 Ecuadorian youths aged 12-17 with measures of SES, language, executive function, and theory of mind (ToM), a.k.a. mentalizing. A subsample gave hair samples to estimate recent cortisol levels. Restricting analyses to reliable measures, SES was highly associated with language skill, and to a lesser extent with executive function and ToM performance. However, those latter associations were attenuated and non-significant when language ability was controlled for statistically. Systemic cortisol levels were not associated with SES, but were significantly and negatively correlated with ToM, independent of variation in language skills. We conclude that language development underlies most of the impact of SES on executive function and ToM ability of adolescents, but that stress-related cortisol may have an independent, direct effect on mentalizing.

A novel µ-conopeptide, CnIIIC, exerts potent and preferential inhibition of NaV1.2/1.4 channels and blocks neuronal nicotinic acetylcholine receptors.

BACKGROUND AND PURPOSE: The µ-conopeptide family is defined by its ability to block voltage-gated sodium channels (VGSCs), a property that can be used for the development of myorelaxants and analgesics. We characterized the pharmacology of a new µ-conopeptide (µ-CnIIIC) on a range of preparations and molecular targets to assess its potential as a myorelaxant. EXPERIMENTAL APPROACH: µ-CnIIIC was sequenced, synthesized and characterized by its direct block of elicited twitch tension in mouse skeletal muscle and action potentials in mouse sciatic and pike olfactory nerves. µ-CnIIIC was also studied on HEK-293 cells expressing various rodent VGSCs and also on voltage-gated potassium channels and nicotinic acetylcholine receptors (nAChRs) to assess cross-interactions. Nuclear magnetic resonance (NMR) experiments were carried out for structural data. KEY RESULTS: Synthetic µ-CnIIIC decreased twitch tension in mouse hemidiaphragms (IC(50) = 150 nM), and displayed a higher blocking effect in mouse extensor digitorum longus muscles (IC = 46 nM), compared with µ-SIIIA, µ-SmIIIA and µ-PIIIA. µ-CnIIIC blocked Na(V)1.4 (IC(50) = 1.3 nM) and Na(V)1.2 channels in a long-lasting manner. Cardiac Na(V)1.5 and DRG-specific Na(V)1.8 channels were not blocked at 1 µM. µ-CnIIIC also blocked the α3ß2 nAChR subtype (IC(50) = 450 nM) and, to a lesser extent, on the α7 and α4ß2 subtypes. Structure determination of µ-CnIIIC revealed some similarities to α-conotoxins acting on nAChRs. CONCLUSION AND IMPLICATIONS: µ-CnIIIC potently blocked VGSCs in skeletal muscle and nerve, and hence is applicable to myorelaxation. Its atypical pharmacological profile suggests some common structural features between VGSCs and nAChR channels.