The inferior colliculus (IC) is a major center of integration in the ascending as well as descending auditory pathways, where both excitatory and inhibitory amino acid neurotransmitters play a key role. When normal input to the auditory system is decreased, the balance between excitation and inhibition in the IC is disturbed. We examined global changes in gene expression in the rat IC 3 and 21 days following bilateral deafening, using Affymetrix GeneChip arrays and focused our analysis on changes in expression of neurotransmission-related genes. Over 1400 probe sets in the Affymetrix Rat Genome U34A Array were identified as genes that were differentially expressed. These genes encoded proteins previously reported to change as a consequence of deafness, such as calbindin, as well as proteins not previously reported to be modulated by deafness, such as clathrin. A subset of 19 differentially expressed genes was further examined using quantitative RT-PCR at 3, 21 and 90 days following deafness. These included several GABA, glycine, glutamate receptor and neuropeptide-related genes.Expression of genes for GABA-A receptor subunits b2, b3, and c2, plus ionotropic glutamate receptor subunits AMPA 2, AMPA 3, and kainate 2, increased at all three times. Expression of glycine receptor a1 initially declined and then later increased, while a2 increased sharply at 21 days. Glycine receptor a3 increased between 3 and 21 days, but decreased at 90 days. Of the neuropeptide-related genes tested with qRT-PCR, tyrosine hydroxylase decreased approximately 50% at all times tested. Serotonin receptor 2C increased at 3, 21, and 90 days. The 5B serotonin receptor decreased at 3 and 21 days and returned to normal by 90 days. Of the genes tested with qRT-PCR, only glycine receptor a2 and serotonin receptor 5B returned to normal levels of expression at 90 days. Changes in GABA receptor b3, GABA receptor c2, glutamate receptor 2/3, enkephalin, and tyrosine hydroxylase were further confirmed using immunocytochemistry.

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After 2-week treatment period, bilastine 20 mg once daily was effective and tolerable in Japanese patients with PAR, and exhibited a rapid onset of action.

There is increasing evidence of activity-related plasticity in auditory pathways. The present study examined the effects of decreased activity on immunolocalization of the inhibitory neurotransmitter glycine in the cochlear nucleus of the rat after bilateral cochlear ablation. Specifically, glycine-immunoreactive puncta adjacent to somatic profiles were compared in normal hearing animals and animals deafened for 14 days. The number of glycine-immunoreactive puncta surrounding somatic profiles of spherical and globular bushy cells, glycineimmunoreactive type I stellate multipolar cells, radiate neurons (type II stellate multipolar cells), and fusiform cells decreased significantly. In addition, the number of glycine immunopositive tuberculoventral (vertical or corn) cells in the deep layer of the dorsal cochlear nucleus also decreased significantly. These results suggest that decreased inhibition reported in cochlear nucleus after deafness may be due to decreases in glycine. Keywords hearing; auditory; ablation; neurotransmitterThere is increasing evidence of plasticity in the mature auditory system, with decreased activity from deafness or increased activity from noise overstimulation capable of inducing marked changes (recently reviewed by Syka, 2002). Activity-induced changes in the auditory brain stem range from changes in gene expression (e.g., Holt et al., 2005) to changes in neuronal response profiles (Francis and Manis, 2000). One of the most striking deafness-related changes in the auditory brain stem is a decrease in inhibition and an increase in spontaneous or evoked excitation, found in both the inferior colliculus (IC) and the cochlear nucleus (CN; Gerken, 1979;Willott and Lu, 1982;Bledsoe et al., 1995;Kaltenbach, 2000;Mossop et al., 2000;Salvi et al., 2000;Willott and Turner, 2000;© 2005 Wiley-Liss, Inc. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptShaddock Palombi et al., 2001), often leading to a change in the tonotopic map Nagase et al., 2000;Snyder et al., 2000). In the IC, the decreased inhibition seems associated with decreases in the inhibitory amino acid neurotransmitter γ-aminobutyric acid (GABA), with studies showing decreased GABA release (Bledsoe et al., 1995) and decreases in the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD) as well as GABA binding (Bauer et al., 2000;Milbrandt et al., 2000;Mossop et al., 2000;Caspary et al., 2002). In the CN, however, many studies suggest that glycine is the major inhibitory transmitter (Altschuler et al., 1986;Wu and Oertel, 1986;Caspary et al., 1987Caspary et al., , 1994Wenthold et al., 1987;Adams and Mugnaini, 1990;Bledsoe et al., 1990;Wickesberg and Oertel, 1990;Helfert et al., 1992;Kolston et al., 1992; Zook, 1992, 1999;Grothe and Sanes, 1993;Wickesberg et al., 1994;Wu and Kelly, 1994;Sato et al., 1995;Golding and Oertel, 1996;Juiz et al., 1996;Harty and Manis, 1998;Doucet et al., 1999;Godfrey et al., 2000;Zheng et al., 2000). Decreases in glycine-immunoreactive neurons and puncta (...