An antidepressant behaviour in mice carrying a gene-specific InsP3R1, InsP3R2 and InsP3R3 protein knockdown
| Autor: | E. Vivoli, M. Norcini, Nicoletta Galeotti, Carla Ghelardini, A. Bartolini |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Macrocyclic Compounds Blotting Western Immunocytochemistry Hippocampus Inositol monophosphatase Motor Activity Biology Mice Cellular and Molecular Neuroscience depression antisense strategy InsP3R1 InsP3R2 InsP3R3 Internal medicine medicine Animals Immunoprecipitation Inositol 1 4 5-Trisphosphate Receptors RNA Messenger Receptor Oxazoles Postural Balance Swimming Injections Intraventricular Brain Chemistry Pharmacology Gene knockdown Behavior Animal Depression Oligonucleotides Antisense Endocrinology Gene Knockdown Techniques biology.protein Antidepressant Lithium Chloride Inositol Intracellular Behavioural despair test |
| Zdroj: | Neuropharmacology. 55:1156-1164 |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/j.neuropharm.2008.07.029 |
| Popis: | Evidence has accumulated for the involvement of Ca2+ in the pathophysiology of mood disorders. Elevations in both resting and stimulated intracellular Ca2+ levels in patients with affective disorders have been reported. The role of inositol-1,4,5-trisphosphate receptors (InsP3Rs), which allow mobilization of intracellular Ca2+ stores, was, then, investigated in the mouse forced swimming test. InsP3R antagonists (heparin, xestospongin C) as well as an inositol monophosphatase inhibitor (LiCl) showed an antidepressant activity of intensity comparable to clinically used antidepressants. InsP3Rl, InsP3R2 and InsP3R3 knockdown mice were obtained to investigate the role of InsP3R isoforms. We generated mice carrying a cerebral knockdown of InsP3Rl, InsP3R2 and InsP3R3 proteins by administering antisense oligonucleotides complementary to the sequence of InsP3Rl, InsP3R2 and InsP3R3. These antisense-treated mice showed a specific InsP3R protein level reduction in the mouse cerebral cortex and hippocampus, demonstrated by immunoblotting, immunoprecipitation and immunocytochemistry experiments. Knockdown mice for each InsP3R isoforms showed an antidepressant behaviour and the induced phenotype was reversible disappearing 7 days after the end of the treatment. The absence of impairment of locomotor activity and spontaneous mobility in InsP3R knockdown mice was revealed. These results indicate the involvement of the InsP3R-mediated pathway in the modulation of depressive conditions and may be useful for the development of new therapeutical strategies for the treatment of mood disorders. |
| Databáze: | OpenAIRE |
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