ABSTRACT
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Subject(s)
Humans , Cadaver , Tissue and Organ Procurement/ethics , Anatomy/ethics , Dissection/ethics , Ethics Committees, Research , Codes of Ethics , Tissue Donors/ethicsABSTRACT
The pattern of expression of ionotropic glutamate receptor (GluR) subunits 1-4 in the medial nucleus of the trapezoid body (MNTB) has been reported to change during development. The aim of this study was to compare the distribution of the GluR1-4 subunits in the MNTB at postnatal day (P) 9, before high-frequency signal transmission in the auditory system has developed, with that observed in mature adult rats. GluR1-4 subunits were studied by preembedding and postembedding immunocytochemical methods. Increased levels of GluR1, 2/3, and 4 associated with development were evident only at postsynaptic sites of MNTB principal cell bodies receiving calyces of Held synapses, whereas receptor density at nonsynaptic sites was found to remain unaltered. Taken together, the expression pattern of GluR subunits and the density of immunoparticles in postsynaptic specializations are indicative of a compartmentalization of alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA) subunits upon development. These developmental changes provide a morphological basis for establishment of the postsynaptic properties needed for high-frequency synaptic transmission of auditory signals to MNTB principal neurons.
Subject(s)
Cochlear Nucleus/cytology , Excitatory Amino Acid Agonists/metabolism , Protein Subunits/metabolism , Receptors, Glutamate/metabolism , Synapses/physiology , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism , Age Factors , Animals , Cochlear Nucleus/growth & development , Immunohistochemistry , Neurons/cytology , Neurons/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
The modulation of ionotropic gamma-aminobutyric acid (GABA) receptors (GABA-gated Cl(-) channels) by a group of natural and synthetic flavonoids was studied in electrophysiological experiments. Quercetin, apigenin, morine, chrysin and flavone inhibited ionic currents mediated by alpha(1)beta(1)gamma(2s) GABA(A) and rho(1) GABA(C) receptors expressed in Xenopus laevis oocytes in the micromolar range. alpha(1)beta(1)gamma(2s) GABA(A) and rho(1) GABA(C) receptors differ largely in their sensitivity to benzodiazepines, but they were similarly modulated by different flavonoids. Quercetin produced comparable actions on currents mediated by alpha(4)beta(2) neuronal nicotinic acetylcholine, serotonin 5-HT(3A) and glutamate AMPA/kainate receptors. Sedative and anxiolytic flavonoids, like chrysin or apigenin, failed to potentiate but antagonized alpha(1)beta(1)gamma(2s) GABA(A) receptors. Effects of apigenin and quercetin on alpha(1)beta(1)gamma(2s) GABA(A) receptors were insensitive to the benzodiazepine antagonist flumazenil. Results indicate that mechanism/s underlying the modulation of ionotropic GABA receptors by some flavonoids differs from that described for classic benzodiazepine modulation.
Subject(s)
Flavonoids/pharmacology , Receptors, GABA-A/physiology , Receptors, GABA/physiology , Animals , Apigenin , Benzoflavones/pharmacology , Female , Humans , Membrane Potentials/drug effects , Microinjections , Oocytes/drug effects , Oocytes/physiology , Quercetin/pharmacology , RNA, Complementary/administration & dosage , RNA, Complementary/genetics , Rats , Receptors, GABA/drug effects , Receptors, GABA/genetics , Receptors, GABA-A/drug effects , Receptors, GABA-A/genetics , Receptors, Neurotransmitter/drug effects , Receptors, Neurotransmitter/genetics , Receptors, Neurotransmitter/physiology , Xenopus laevisABSTRACT
The parasagittal distribution of the splice variant 1b of the metabotropic glutamate receptor 1 (mGluR1b) was studied in the cerebellar cortex by using a specific mGluR1b antiserum combined with immunocytochemical methods. In frontal cerebellar sections, the antibodies revealed alternating bands of immunopositive and immunonegative Purkinje cells in lobules I to X of the vermis. In these regions, the distribution of mGluR1b was complementary to longitudinal bands of Purkinje cells expressing Zebrin II. The width of the mGluR1b-positive bands decreased progressively in the rostro-caudal direction, contrary to the rostro-caudal increase in the width of the Zebrin-positive bands. In the hemispheres, mGluR1b-positive bands alternated with Zebrin II-immunopositive bands in the paravermal portions of Crus I and Crus II. MGluR1b and Zebrin II immunoreactivities often colocalized in other regions of the hemispheral lobules. The compartmentalization of mGluR1b suggests that adjacent Purkinje cells might respond differently depending on the presence of mGluR1b at parallel fiber-Purkinje cell synapses (AU)
Ha sido estudiada la distribución parasagital de la variante 1b de unión del receptor 1 metabotrópico de glutamato (mGluR1b) en la corteza cerebelosa, utilizando un antisuero mGluR1b en combinación con métodos inmunocitoquímicos. En secciones frontales del cerebelo, los anticuerpos revelaron la existencia de bandas alternantes de células de Purkinje inmunopositivas e inmunonegativas en los lóbulos I al X del vermis. En estas regiones, la distribución de mGluR1b era complementaria a bandas longitudinales de células de Purkinje que expresaban zebrina II.La anchura de las bandas mGluR1b-positivas decreció progresivamente en dirección rostro-caudal, a diferencia del aumento rostro-caudal en la anchura de las bandas zebrina-positivas. En los hemisferios, bandas mGluR1b-positivas alternaban con bandas zebrina II-inmunopositivas en las porciones paravermianas de Crus I y Crus II. Las inmunoreactividades de mGluR1b y zebrina II frecuentemente colocalizaban en otras regiones de los lóbulos de los hemisferios.La compartimentación de mGluR1b sugiere que es posible que las células de Purkinje adyacentes respondan de manera diferente, dependiendo de la presencia de mGluR1b en las sinapsis de las células de fibras paralelas (AU)
