Ryanodine receptor-2 upregulation and nicotine-mediated plasticity
Autor: | Pierluigi Nicotera, Daniele Bano, Kenneth W. Young, Stefania Guiducci, Elena Ziviani, Giordano Lippi, Eliana Munarriz, Michele Zoli |
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Rok vydání: | 2010 |
Předmět: |
medicine.medical_specialty
General Immunology and Microbiology Ryanodine receptor General Neuroscience Biology CREB Ryanodine receptor 2 General Biochemistry Genetics and Molecular Biology Cell biology Nicotine Endocrinology Downregulation and upregulation Internal medicine Cerebellar cortex medicine biology.protein Premovement neuronal activity Molecular Biology medicine.drug Calcium signaling |
Zdroj: | The EMBO Journal. 30:194-204 |
ISSN: | 0261-4189 |
Popis: | Nicotine, the major psychoactive component of cigarette smoke, modulates neuronal activity to produce Ca2+-dependent changes in gene transcription. However, the downstream targets that underlie the long-term effects of nicotine on neuronal function, and hence behaviour, remain to be elucidated. Here, we demonstrate that nicotine administration to mice upregulates levels of the type 2 ryanodine receptor (RyR2), a Ca2+-release channel present on the endoplasmic reticulum, in a number of brain areas associated with cognition and addiction, notably the cortex and ventral midbrain. Nicotine-mediated RyR2 upregulation was driven by CREB, and caused a long-lasting reinforcement of Ca2+ signalling via the process of Ca2+-induced Ca2+ release. RyR2 upregulation was itself required for long-term phosphorylation of CREB in a positive-feedback signalling loop. We further demonstrate that inhibition of RyR-activation in vivo abolishes sensitization to nicotine-induced habituated locomotion, a well-characterised model for onset of drug dependence. Our findings, therefore, indicate that gene-dependent reprogramming of Ca2+ signalling is involved in nicotine-induced behavioural changes. |
Databáze: | OpenAIRE |
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