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Expression of serotonin 5‐HT 2A receptors in the human cerebellum and alterations in schizophrenia
Author(s) -
Eastwood Sharon L.,
Burnet Philip W.J.,
Gittins Rebecca,
Baker Kate,
Harrison Paul J.
Publication year - 2001
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.1106
Subject(s) - ketanserin , cerebellum , serotonin , receptor , medicine , endocrinology , 5 ht receptor , schizophrenia (object oriented programming) , purkinje cell , blot , biology , 5 ht2a receptor , microbiology and biotechnology , neuroscience , psychology , gene , biochemistry , psychiatry
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 ∼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. Synapse 42:104–114, 2001. © 2001 Wiley‐Liss, Inc.