An antidepressant behaviour in mice carrying a gene-specific InsP3R1, InsP3R2 and InsP3R3 protein knockdown

Neuropharmacology
Nicoletta GaleottiCarla Ghelardini

Abstract

Evidence has accumulated for the involvement of Ca(2+) in the pathophysiology of mood disorders. Elevations in both resting and stimulated intracellular Ca(2+) levels in patients with affective disorders have been reported. The role of inositol-1,4,5-trisphosphate receptors (InsP3Rs), which allow mobilization of intracellular Ca(2+) 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 aft...Continue Reading

References

May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·C A RossA Ullrich
Oct 15, 1992·Biological Psychiatry·I KusumiI Yamashita
Jan 1, 1991·Progress in Neuro-psychopharmacology & Biological Psychiatry·M MikuniK Takahashi
Jan 1, 1994·European Archives of Psychiatry and Clinical Neuroscience·S L DubovskyJ Murphy
Jan 28, 1993·Nature·M J Berridge
Apr 15, 1996·Biological Psychiatry·F KaregeJ M Gaillard
Jun 1, 1996·Neurodegeneration : a Journal for Neurodegenerative Disorders, Neuroprotection, and Neuroregeneration·L S HaugS I Walaas
Jul 1, 1997·The American Journal of Psychiatry·M EmamghoreishiJ J Warsh
Jun 1, 1997·Current Opinion in Neurobiology·K Mikoshiba
Nov 25, 1997·Annals of the New York Academy of Sciences·S JonasR Llinás
Aug 11, 1998·Neuron·M J Berridge
Apr 23, 1999·Early Human Development·N ZecevicB E Ehrlich
Jun 23, 1999·Cell Calcium·S PatelA P Thomas
Jul 30, 1999·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·M Matsumoto, E Nagata
Feb 11, 2000·Cell Calcium·C W TaylorS A Morris
Aug 16, 2000·Cell Calcium·L MissiaenH De Smedt
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·C J Phiel, P S Klein
Dec 20, 2002·General Hospital Psychiatry·Salvador Sarro MaluquerLuis San
May 9, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Nicoletta GaleottiCarla Ghelardini
Aug 12, 2003·Cell Calcium·Mark P Mattson, Sic L Chan
Dec 20, 2003·The EMBO Journal·Nael Nadif KasriH Llewelyn Roderick
Dec 21, 2004·Psychopharmacology·Benoit Petit-DemouliereMichel Bourin
Oct 1, 2005·Science·Akira FutatsugiKatsuhiko Mikoshiba
May 13, 2006·The Journal of Clinical Investigation·Christina SchleckerBarbara E Ehrlich
Apr 13, 2007·Physiological Reviews·J Kevin FoskettDon-On Daniel Mak
May 18, 2007·Annual Review of Biochemistry·Ran ZalkAndrew R Marks

❮ Previous
Next ❯

Citations

Oct 5, 2010·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Francesco CasamassimaRoy H Perlis
May 23, 2014·Revista brasileira de psiquiatria : orgão oficial da Associação Brasileira de Psiquiatria, Asociación Psiquiátrica de la América Latina·Emilio L StreckJoão Quevedo
Apr 19, 2012·Nature Reviews. Neuroscience·Husseini ManjiGuang Chen
Feb 17, 2017·Pharmacological Reviews·Michael J Berridge
Dec 8, 2015·Biological Chemistry·Tsvetan SerchovKnut Biber
May 11, 2021·Expert Opinion on Investigational Drugs·Marguerite Le MaroisRaoul Belzeaux
Mar 14, 2020·The European Journal of Neuroscience·Sónia Guerra-GomesJoão Filipe Oliveira

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Antisense Oligonucleotide Therapies: ND

Antisense oligonucleotides are synthetic DNA oligomers that hybridize to a target RNA. This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases.

Ataxias

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on different types of ataxias here.

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Ataxias (MDS)

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Ataxia

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.