Expression of serotonin 5-HT(2A) receptors in the human cerebellum and alterations in schizophrenia.

The occurrence of human cerebellar serotonin 5-HT(2A) receptors (5-HT(2A)R) is equivocal and their status in schizophrenia unknown. Using a range of techniques, we investigated cerebellar 5-HT(2A)R expression in 16 healthy subjects and 16 subjects with schizophrenia. Immunocytochemistry with a monoc...

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Autori principali: Eastwood, S, Burnet, P, Gittins, R, Baker, K, Harrison, P
Natura: Journal article
Lingua:English
Pubblicazione: 2001
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author Eastwood, S
Burnet, P
Gittins, R
Baker, K
Harrison, P
author_facet Eastwood, S
Burnet, P
Gittins, R
Baker, K
Harrison, P
author_sort Eastwood, S
collection OXFORD
description The occurrence of human cerebellar serotonin 5-HT(2A) receptors (5-HT(2A)R) is equivocal and their status in schizophrenia unknown. Using a range of techniques, we investigated cerebellar 5-HT(2A)R expression in 16 healthy subjects and 16 subjects with schizophrenia. Immunocytochemistry with a monoclonal antibody showed labelling of Purkinje cell bodies and dendrites, as well as putative astrocytes. Western blots showed a major band at approximately 45 kDa. Receptor autoradiography and homogenate binding with [(3)H]ketanserin revealed cerebellar 5-HT(2A)R binding sites present at levels approximately a third of that in prefrontal cortex. 5-HT(2A)R mRNA was detected by reverse transcriptase-polymerase chain reaction, with higher relative levels in men than women. Several aspects of 5-HT(2A)R expression were altered in schizophrenia. 5-HT(2A)R immunoreactivity in Purkinje cells was partially redistributed from soma to dendrites and was increased in white matter. 5-HT(2A)R mRNA was decreased in the male patients. 5-HT(2A)R measured by dot blots and [(3)H]ketanserin binding (B(max) and K(d)) were not significantly altered in schizophrenia. These data show that 5-HT(2A)R gene products (mRNA, protein, binding sites) are expressed in the human cerebellum at nonnegligible levels; this bears upon 5-HT(2A)R imaging studies which use the cerebellum as a reference region. 5-HT(2A)R expression is altered in schizophrenia; the shift of 5-HT(2A)R from soma to dendrites is noteworthy since atypical antipsychotics have the opposite effect. Finally, the results emphasise that expression of a receptor gene is a mutifaceted process. Measurement of multiple parameters is necessary to give a clear picture of the normal situation and to show the profile of alterations in a disease.
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spelling oxford-uuid:a5217155-aaa9-4bb2-bc2e-dece0147e5c12022-03-27T02:38:17ZExpression of serotonin 5-HT(2A) receptors in the human cerebellum and alterations in schizophrenia.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a5217155-aaa9-4bb2-bc2e-dece0147e5c1EnglishSymplectic Elements at Oxford2001Eastwood, SBurnet, PGittins, RBaker, KHarrison, PThe occurrence of human cerebellar serotonin 5-HT(2A) receptors (5-HT(2A)R) is equivocal and their status in schizophrenia unknown. Using a range of techniques, we investigated cerebellar 5-HT(2A)R expression in 16 healthy subjects and 16 subjects with schizophrenia. Immunocytochemistry with a monoclonal antibody showed labelling of Purkinje cell bodies and dendrites, as well as putative astrocytes. Western blots showed a major band at approximately 45 kDa. Receptor autoradiography and homogenate binding with [(3)H]ketanserin revealed cerebellar 5-HT(2A)R binding sites present at levels approximately a third of that in prefrontal cortex. 5-HT(2A)R mRNA was detected by reverse transcriptase-polymerase chain reaction, with higher relative levels in men than women. Several aspects of 5-HT(2A)R expression were altered in schizophrenia. 5-HT(2A)R immunoreactivity in Purkinje cells was partially redistributed from soma to dendrites and was increased in white matter. 5-HT(2A)R mRNA was decreased in the male patients. 5-HT(2A)R measured by dot blots and [(3)H]ketanserin binding (B(max) and K(d)) were not significantly altered in schizophrenia. These data show that 5-HT(2A)R gene products (mRNA, protein, binding sites) are expressed in the human cerebellum at nonnegligible levels; this bears upon 5-HT(2A)R imaging studies which use the cerebellum as a reference region. 5-HT(2A)R expression is altered in schizophrenia; the shift of 5-HT(2A)R from soma to dendrites is noteworthy since atypical antipsychotics have the opposite effect. Finally, the results emphasise that expression of a receptor gene is a mutifaceted process. Measurement of multiple parameters is necessary to give a clear picture of the normal situation and to show the profile of alterations in a disease.
spellingShingle Eastwood, S
Burnet, P
Gittins, R
Baker, K
Harrison, P
Expression of serotonin 5-HT(2A) receptors in the human cerebellum and alterations in schizophrenia.
title Expression of serotonin 5-HT(2A) receptors in the human cerebellum and alterations in schizophrenia.
title_full Expression of serotonin 5-HT(2A) receptors in the human cerebellum and alterations in schizophrenia.
title_fullStr Expression of serotonin 5-HT(2A) receptors in the human cerebellum and alterations in schizophrenia.
title_full_unstemmed Expression of serotonin 5-HT(2A) receptors in the human cerebellum and alterations in schizophrenia.
title_short Expression of serotonin 5-HT(2A) receptors in the human cerebellum and alterations in schizophrenia.
title_sort expression of serotonin 5 ht 2a receptors in the human cerebellum and alterations in schizophrenia
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