Expression of serotonin 5‐HT2A receptors in the human cerebellum and alterations in schizophrenia

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Abstract
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 ∼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 [3H]ketanserin binding (Bmax and Kd) 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. Synapse 42:104–114, 2001.