Journal
SYNAPSE
Volume 42, Issue 2, Pages 104-114Publisher
WILEY
DOI: 10.1002/syn.1106
Keywords
autoradiography; immunoautoradiography; immunocytochemistry; ketanserin; mRNA; RT-PCR; serotonin-2A
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The occurrence of human cerebellar serotonin 5-HT2A receptors (5-HT2AR) is equivocal and their status in schizophrenia unknown. Using a range of techniques, we investigated cerebellar 5-HT2AR 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 similar to 45 kDa. Receptor autoradiography and homogenate binding with [3H]ketanserin revealed cerebellar 5-HT2AR binding sites present at levels approximately a third of that in prefrontal cortex. 5-HT2AR mRNA was detected by reverse transcriptase-polymerase chain reaction, with higher relative levels in men than women. Several aspects of 5-HT2AR expression were altered in schizophrenia. 5-HT2AR immunoreactivity in Purkinje cells was partially redistributed from soma to dendrites and was increased in white matter. 5-HT2AR mRNA was decreased in the male patients. 5-HT2AR measured by dot blots and [H-3]ketanserin binding (B-max and K-d) were not significantly altered in schizophrenia. These data show that 5-HT2AR gene products (mRNA, protein, binding sites) are expressed in the human cerebellum at nonnegligible levels; this bears upon 5-HT2AR imaging studies which use the cerebellum as a reference region. 5-HT2AR expression is altered in schizophrenia; the shift of 5-HT2AR 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. (C) 2001 Wiley-Liss, Inc.
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