Neuron specific alpha-adrenergic receptor expression in human cerebellum: Implications for emerging cerebellar roles in neurologic disease.

摘要

Recent data suggest novel functional roles for cerebellar involvement in a number of neurologic diseases. Function of cerebellar neurons is known to be modulated by norepinephrine and adrenergic receptors. The distribution of adrenergic receptor subtypes has been described in experimental animals, but corroboration of such studies in the human cerebellum, necessary for drug treatment, is still lacking. In the present work we studied cell-specific localizations of alpha(1) adrenergic receptor subtype mRNA (alpha(1a), alpha(1b), alpha(1d)), and alpha(2) adrenergic receptor subtype mRNA (alpha(2a), alpha(2b), alpha(2c)) by in situ hybridization on cryostat sections of human cerebellum (cortical layers and dentate nucleus). We observed unique neuron-specific alpha(1) adrenergic receptor and alpha(2) adrenergic receptor subtype distribution in human cerebellum. The cerebellar cortex expresses mRNA encoding all six alpha adrenergic receptor subtypes, whereas dentate nucleus neurons express all subtype mRNAs,except alpha(2a) adrenergic receptor mRNA. All Purkinje cells label strongly for alpha(2a) and alpha(2b) adrenergic receptor mRNA. Additionally, Purkinje cells of the anterior lobe vermis (lobules I to V) and uvula/tonsil (lobules IX/HIX) express alpha(1a) and alpha(2c) subtypes, and Purkinje cells in the ansiform lobule (lobule HVII) and uvula/tonsil express alpha(1b) and alpha(2c) adrenergic receptor subtypes. Basket cells show a strong signal for alpha(1a), moderate signal for alpha(2a) and light label for alpha(2b) adrenergic receptor mRNA. In stellate cells, besides a strong label of alpha(2a) adrenergic receptor mRNA in all and moderate label of alpha(2b) message in select stellate cells, the inner stellate cells are also moderately positive for alpha(1b) adrenergic receptor mRNA. Granule and Golgi cells express high levels of alpha(2a) and alpha(2b) adrenergic receptor mRNAs. These data contribute new information regarding specific location of adrenergic receptor subtypes in human cerebellar neurons. We discuss our observations in terms of possible modulatory roles of adrenergic receptor subtypes in cerebellar neurons responding to sensory and autonomic input signals, and review species differences in cerebellar adrenergic receptor expression.