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...
| Autori principali: | , , , , |
|---|---|
| Natura: | Journal article |
| Lingua: | English |
| Pubblicazione: |
2001
|
| _version_ | 1826289149823418368 |
|---|---|
| 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. |
| first_indexed | 2024-03-07T02:24:30Z |
| format | Journal article |
| id | oxford-uuid:a5217155-aaa9-4bb2-bc2e-dece0147e5c1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:24:30Z |
| publishDate | 2001 |
| record_format | dspace |
| 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 |
| work_keys_str_mv | AT eastwoods expressionofserotonin5ht2areceptorsinthehumancerebellumandalterationsinschizophrenia AT burnetp expressionofserotonin5ht2areceptorsinthehumancerebellumandalterationsinschizophrenia AT gittinsr expressionofserotonin5ht2areceptorsinthehumancerebellumandalterationsinschizophrenia AT bakerk expressionofserotonin5ht2areceptorsinthehumancerebellumandalterationsinschizophrenia AT harrisonp expressionofserotonin5ht2areceptorsinthehumancerebellumandalterationsinschizophrenia |