Frontiers in pediatrics
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Frontiers in pediatrics · Jan 2014
ReviewGABAergic signaling as therapeutic target for autism spectrum disorders.
γ-Aminobutyric acid (GABA), the main inhibitory neurotransmitter in the adult brain, early in postnatal life exerts a depolarizing and excitatory action. This depends on accumulation of chloride inside the cell via the cation-chloride importer NKCC1, being the expression of the chloride exporter KCC2 very low at birth. The developmentally regulated expression of KCC2 results in extrusion of chloride with age and a shift of GABA from the depolarizing to the hyperpolarizing direction. ⋯ In this review, we will discuss how changes of GABAA-mediated neurotransmission affect several forms of ASDs including the Fragile X, the Angelman, and Rett syndromes. Then, we will describe various animal models of ASDs with GABAergic dysfunctions, highlighting their behavioral deficits and the possibility to rescue them by targeting selective components of the GABAergic synapse. In particular, we will discuss how in some cases, reverting the polarity of GABA responses from the depolarizing to the hyperpolarizing direction with the diuretic bumetanide, a selective blocker of NKCC1, may have beneficial effects on ASDs, thus opening new therapeutic perspectives for the treatment of these devastating disorders.
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Frontiers in pediatrics · Jan 2014
ReviewHow Pediatric Urology Fellowships in the United States are Funded.
We desired to discover how pediatric urology fellowship positions in the United States were funded. ⋯ All but three hospitals fund 100% of the clinical year of pediatric urology fellowship. Sources of funding for the second, ABU-required year vary widely among fellowship programs in the United States.