Regulation of tyrosine hydroxylase expression in tottering mouse Purkinje cells. 2003

Brandy E Fureman, and Daniel B Campbell, and Ellen J Hess
Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.

Tottering (tg) mice inherit a missense mutation in the Alpha1A subunit of P/Q-type calcium channels. This mutation results in an increased density of L-type calcium channels in the cerebellum and abnormal regulation of tyrosine hydroxylase (TH) gene expression in a subset of cerebellar Purkinje cells, a cell type that does not normally express TH. The behavioral phenotype includes attacks of dyskinesia, which can be blocked by L-type calcium channel antagonists. To test the hypothesis that cerebellar TH mRNA expression can be manipulated in vivo by L-type calcium channel blockade, control and tottering mice were chronically treated with the L-type calcium channel antagonist nimodipine. Chronic nimodipine treatment significantly reduced the expression of TH mRNA in tottering mouse Purkinje cells. This effect was observed without altering the increased density of L-type calcium channels in tottering mouse cerebella. Chronic nimodipine treatment had no effect on TH mRNA expression in tottering mouse catecholaminergic neurons, including those of the locus coeruleus and substantia nigra. However, a small reduction in TH mRNA expression in the substantia nigra of control mice was observed after drug treatment. These data suggest that the abnormal expression of TH in tottering mouse Purkinje cells is regulated by Purkinje cell excitability.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008818 Mice, Neurologic Mutants Mice which carry mutant genes for neurologic defects or abnormalities. Lurcher Mice,Nervous Mice,Reeler Mice,Staggerer Mice,Weaver Mice,Chakragati Mice,Chakragati Mouse,Lurcher Mouse,Mice, Neurological Mutants,Mouse, Neurologic Mutant,Mouse, Neurological Mutant,Nervous Mouse,Neurologic Mutant Mice,Neurological Mutant Mouse,Reeler Mouse,Staggerer Mouse,Weaver Mouse,ckr Mutant Mice,Mice, Chakragati,Mice, Lurcher,Mice, Nervous,Mice, Neurologic Mutant,Mice, Reeler,Mice, Staggerer,Mice, Weaver,Mice, ckr Mutant,Mouse, Chakragati,Mouse, Lurcher,Mouse, Nervous,Mouse, Reeler,Mouse, Staggerer,Mouse, Weaver,Mutant Mice, Neurologic,Mutant Mice, ckr,Mutant Mouse, Neurologic,Neurologic Mutant Mouse
D009553 Nimodipine A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure. Admon,Bay e 9736,Brainal,Calnit,Kenesil,Modus,Nimodipin Hexal,Nimodipin-ISIS,Nimodipino Bayvit,Nimotop,Nymalize,Remontal,Bayvit, Nimodipino,Hexal, Nimodipin,Nimodipin ISIS,e 9736, Bay
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011689 Purkinje Cells The output neurons of the cerebellar cortex. Purkinje Cell,Purkinje Neuron,Purkyne Cell,Cell, Purkinje,Cell, Purkyne,Cells, Purkinje,Cells, Purkyne,Neuron, Purkinje,Neurons, Purkinje,Purkinje Neurons,Purkyne Cells
D002121 Calcium Channel Blockers A class of drugs that act by selective inhibition of calcium influx through cellular membranes. Calcium Antagonists, Exogenous,Calcium Blockaders, Exogenous,Calcium Channel Antagonist,Calcium Channel Blocker,Calcium Channel Blocking Drug,Calcium Inhibitors, Exogenous,Channel Blockers, Calcium,Exogenous Calcium Blockader,Exogenous Calcium Inhibitor,Calcium Channel Antagonists,Calcium Channel Blocking Drugs,Exogenous Calcium Antagonists,Exogenous Calcium Blockaders,Exogenous Calcium Inhibitors,Antagonist, Calcium Channel,Antagonists, Calcium Channel,Antagonists, Exogenous Calcium,Blockader, Exogenous Calcium,Blocker, Calcium Channel,Blockers, Calcium Channel,Calcium Blockader, Exogenous,Calcium Inhibitor, Exogenous,Channel Antagonist, Calcium,Channel Blocker, Calcium,Inhibitor, Exogenous Calcium
D002531 Cerebellum The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills. Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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