Brain research
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Neurosteroids are potent, endogenous modulators of GABAA receptor function in the central nervous system. The endogenous progesterone metabolite allopregnanolone (ALP) and the synthetic steroid compound alphaxalone (AFX) have been shown to both directly activate and potentiate GABAA receptor-activated membrane current (IGABA). The role of different alpha and gamma subunit subtypes in modulation of IGABA by ALP and AFX was investigated using recombinant GABAA receptor isoforms expressed in Xenopus oocytes. ⋯ This study provides evidence that the alpha subunit subtype determines the efficacy, but not the potency, of these neuroactive steroids to potentiate IGABA. The gamma3 subunit subtype increases the maximal efficacy of neuroactive steroids compared to other gamma subunit subtypes. These results suggest that the heteromeric assembly of different GABAA receptor isoforms containing different subunit subtypes results in multiple steroid recognition sites on GABAA receptors that in turn produce distinctly different modulatory interactions between neuroactive steroids acting at the GABAA receptor.
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Comparative Study
Human somatosensory cortical activation strengths: comparison between males and females and age-related changes.
The amplitudes of many scalp-recorded evoked potential (EP) deflections are higher in females than in males, and in elderly than in young subjects. Since EPs critically depend on the electric conductivity of the cranium, it is not known whether these differences reflect age- and gender-dependent changes in the intensity of neuronal activation, or changes in the volume conductor. Evoked magnetic fields are not significantly affected by the conductivities of the cranial tissues and therefore reflect more directly the neuronal activation than EPs. ⋯ The N20m ECD strength showed a significant positive correlation (r=0.39, p<0.01) with age while P35m and P60m ECD strengths did not. The results thus did not disclose gender differences in the activation strengths of the somatosensory cortex, implying that such differences in evoked potentials may possibly be due to gender differences in the volume conductor. On the other hand, the results suggest a slight age-related increase in cortical excitability.