The present investigation was designed to determine the central sensory neuronal pathways and their GABA(A)-alpha 1 and -alpha 3 receptor presenting neurons that respond to gastric mechanoreceptor stimulation within the entire rat brain. Low pressure gastric distension was used to deliver physiological mechanical stimuli in anesthetized rats, and different protocols PD0332991 supplier of gastric distension were performed to mimic different stimulation patterns with and without sectioning vagal and/or splanchnic afferent nerves. Mapping of activated neurons was investigated using double colorimetric immunolhistochemistry for GABA(A)-alpha 1 or -alpha 3 subunits and c-Fos. Following

stomach distension, neurons expressing GABA(A) receptors with alpha 1 or alpha 3 subunits were detected. Low frequency gastric distension induced c-Fos expression in nucleus tractus solitarii

(NTS) only, whereas in the high frequency gastric distension c-Fos positive nuclei were found in lateral reticular nucleus and in NTS in addition to some forebrain areas. In contrast, during the tonic-rapid gastric distension the neuronal see more activation was found in hindbrain, midbrain and forebrain areas. Moreover different protocols of gastric stimulation activated diverse patterns of neurons presenting GABA(A)-alpha 1 or -alpha 3 receptors within responding brain nuclei, which may indicate a probable functional significance of differential expression of GABAA-responding neurons. The same protocol of gastric Pritelivir distension performed in vagotomized rats has confirmed the primary role of the vagus in the response of activation of gastric brain areas, whereas neuronal input of splanchnic origins was shown to play an important role in modulating the mechanogastric response of brain areas. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“A disintegrin and metalloprotease (ADAM) 10 is the main candidate enzyme

for the a-secretase processing of the amyloid precursor protein (APP). Neuron-specific ADAM10 overexpression proved beneficial in the APP[V7171] mutant Alzheimer mouse model [Postina R, Schroeder A, Dewachter I, Bohl J, Schmitt U, Kojro E, Prinzen C, Endres K, Hiemke C, Blessing M, Flamez P, Dequenne A, Godaux E, van Leuven F, Fahrenholz F (2004) A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Invest 113:1456-1464]. Since Alzheimer patients have a high prevalence for epileptic seizures, we investigated the effects of ADAM10 modulation under conditions of experimentally induced epileptic seizures. In this context we also examined whether ADAM10 effects were influenced by APP levels. Therefore we compared severity of kainate-induced seizures, neurodegeneration and inflammation in double transgenic mice overexpressing functional ADAM10 or a dominant negative ADAM10 mutant in the APP[V7171] background with single transgenic ADAM10 modulated mice.