Plasticity of histamine H<sub>3 </sub>receptor expression and binding in the vestibular nuclei after labyrinthectomy in rat

<p>Abstract</p> <p>Background</p> <p>In rat, deafferentation of one labyrinth (unilateral labyrinthectomy) results in a characteristic syndrome of ocular and motor postural disorders (e.g., barrel rotation, circling behavior, and spontaneous nystagmus). Behavioral recov...

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Main Authors: Karlstedt Kaj, Aarnisalo Antti A, Lozada Adrian F, Stark Holger, Panula Pertti
Format: Article
Language:English
Published: BMC 2004-09-01
Series:BMC Neuroscience
Online Access:http://www.biomedcentral.com/1471-2202/5/32
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author Karlstedt Kaj
Aarnisalo Antti A
Lozada Adrian F
Stark Holger
Panula Pertti
author_facet Karlstedt Kaj
Aarnisalo Antti A
Lozada Adrian F
Stark Holger
Panula Pertti
author_sort Karlstedt Kaj
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>In rat, deafferentation of one labyrinth (unilateral labyrinthectomy) results in a characteristic syndrome of ocular and motor postural disorders (e.g., barrel rotation, circling behavior, and spontaneous nystagmus). Behavioral recovery (e.g., diminished symptoms), encompassing 1 week after unilateral labyrinthectomy, has been termed vestibular compensation. Evidence suggesting that the histamine H<sub>3 </sub>receptor plays a key role in vestibular compensation comes from studies indicating that betahistine, a histamine-like drug that acts as both a partial histamine H<sub>1 </sub>receptor agonist and an H<sub>3 </sub>receptor antagonist, can accelerate the process of vestibular compensation.</p> <p>Results</p> <p>Expression levels for histamine H<sub>3 </sub>receptor (total) as well as three isoforms which display variable lengths of the third intracellular loop of the receptor were analyzed using <it>in situ </it>hybridization on brain sections containing the rat medial vestibular nucleus after unilateral labyrinthectomy. We compared these expression levels to H<sub>3 </sub>receptor binding densities.</p> <p>Total H<sub>3 </sub>receptor mRNA levels (detected by oligo probe H<sub>3X</sub>) as well as mRNA levels of the three receptor isoforms studied (detected by oligo probes H<sub>3A</sub>, H<sub>3B</sub>, and H<sub>3C</sub>) showed a pattern of increase, which was bilaterally significant at 24 h post-lesion for both H<sub>3X </sub>and H<sub>3C</sub>, followed by significant bilateral decreases in medial vestibular nuclei occurring 48 h (H<sub>3X </sub>and H<sub>3B</sub>) and 1 week post-lesion (H<sub>3A</sub>, H<sub>3B</sub>, and H<sub>3C</sub>). Expression levels of H<sub>3B </sub>was an exception to the forementioned pattern with significant decreases already detected at 24 h post-lesion. Coinciding with the decreasing trends in H<sub>3 </sub>receptor mRNA levels was an observed increase in H<sub>3 </sub>receptor binding densities occurring in the ipsilateral medial vestibular nuclei 48 h post-lesion.</p> <p>Conclusion</p> <p>Progressive recovery of the resting discharge of the deafferentated medial vestibular nuclei neurons results in functional restoration of the static postural and occulomotor deficits, usually occurring within a time frame of 48 hours in rats. Our data suggests that the H<sub>3</sub> receptor may be an essential part of pre-synaptic mechanisms required for reestablishing resting activities 48 h after unilateral labyrinthectomy.</p>
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spelling doaj.art-2d73f7ce7bd04279903449951fc0f3b22022-12-22T00:24:38ZengBMCBMC Neuroscience1471-22022004-09-01513210.1186/1471-2202-5-32Plasticity of histamine H<sub>3 </sub>receptor expression and binding in the vestibular nuclei after labyrinthectomy in ratKarlstedt KajAarnisalo Antti ALozada Adrian FStark HolgerPanula Pertti<p>Abstract</p> <p>Background</p> <p>In rat, deafferentation of one labyrinth (unilateral labyrinthectomy) results in a characteristic syndrome of ocular and motor postural disorders (e.g., barrel rotation, circling behavior, and spontaneous nystagmus). Behavioral recovery (e.g., diminished symptoms), encompassing 1 week after unilateral labyrinthectomy, has been termed vestibular compensation. Evidence suggesting that the histamine H<sub>3 </sub>receptor plays a key role in vestibular compensation comes from studies indicating that betahistine, a histamine-like drug that acts as both a partial histamine H<sub>1 </sub>receptor agonist and an H<sub>3 </sub>receptor antagonist, can accelerate the process of vestibular compensation.</p> <p>Results</p> <p>Expression levels for histamine H<sub>3 </sub>receptor (total) as well as three isoforms which display variable lengths of the third intracellular loop of the receptor were analyzed using <it>in situ </it>hybridization on brain sections containing the rat medial vestibular nucleus after unilateral labyrinthectomy. We compared these expression levels to H<sub>3 </sub>receptor binding densities.</p> <p>Total H<sub>3 </sub>receptor mRNA levels (detected by oligo probe H<sub>3X</sub>) as well as mRNA levels of the three receptor isoforms studied (detected by oligo probes H<sub>3A</sub>, H<sub>3B</sub>, and H<sub>3C</sub>) showed a pattern of increase, which was bilaterally significant at 24 h post-lesion for both H<sub>3X </sub>and H<sub>3C</sub>, followed by significant bilateral decreases in medial vestibular nuclei occurring 48 h (H<sub>3X </sub>and H<sub>3B</sub>) and 1 week post-lesion (H<sub>3A</sub>, H<sub>3B</sub>, and H<sub>3C</sub>). Expression levels of H<sub>3B </sub>was an exception to the forementioned pattern with significant decreases already detected at 24 h post-lesion. Coinciding with the decreasing trends in H<sub>3 </sub>receptor mRNA levels was an observed increase in H<sub>3 </sub>receptor binding densities occurring in the ipsilateral medial vestibular nuclei 48 h post-lesion.</p> <p>Conclusion</p> <p>Progressive recovery of the resting discharge of the deafferentated medial vestibular nuclei neurons results in functional restoration of the static postural and occulomotor deficits, usually occurring within a time frame of 48 hours in rats. Our data suggests that the H<sub>3</sub> receptor may be an essential part of pre-synaptic mechanisms required for reestablishing resting activities 48 h after unilateral labyrinthectomy.</p>http://www.biomedcentral.com/1471-2202/5/32
spellingShingle Karlstedt Kaj
Aarnisalo Antti A
Lozada Adrian F
Stark Holger
Panula Pertti
Plasticity of histamine H<sub>3 </sub>receptor expression and binding in the vestibular nuclei after labyrinthectomy in rat
BMC Neuroscience
title Plasticity of histamine H<sub>3 </sub>receptor expression and binding in the vestibular nuclei after labyrinthectomy in rat
title_full Plasticity of histamine H<sub>3 </sub>receptor expression and binding in the vestibular nuclei after labyrinthectomy in rat
title_fullStr Plasticity of histamine H<sub>3 </sub>receptor expression and binding in the vestibular nuclei after labyrinthectomy in rat
title_full_unstemmed Plasticity of histamine H<sub>3 </sub>receptor expression and binding in the vestibular nuclei after labyrinthectomy in rat
title_short Plasticity of histamine H<sub>3 </sub>receptor expression and binding in the vestibular nuclei after labyrinthectomy in rat
title_sort plasticity of histamine h sub 3 sub receptor expression and binding in the vestibular nuclei after labyrinthectomy in rat
url http://www.biomedcentral.com/1471-2202/5/32
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