Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-1-29
pubmed:abstractText
Calcineurin (PP2B) is a Ca(2+)-dependent protein phosphatase enriched in the brain that takes part in intracellular signaling pathways regulating synaptic plasticity and neuronal functions. Calcineurin-dependent pathways are important for complex brain functions such as learning and memory. More recently, they have been suggested to play a role in the processing of emotional information. The aim of this study was to investigate whether calcineurin may be involved in the effect of antidepressants. We first found that chronic antidepressant treatment in mice leads to an increase of calcineurin levels in the hippocampus. We then studied the behavioral and molecular responses to fluoxetine of mice with a genetic overactivation of calcineurin in the hippocampus (constitutively-activated calcineurin transgenic mouse line #98, CN98 mice). We observed that CN98 mice are more sensitive to the behavioral effect of fluoxetine and desipramine tested in the tail suspension test. Moreover, the basal expression of growth factor brain-derived neurotrophic factor and subunit 1 of AMPA glutamate receptor, GluR1, both of which are modified after chronic antidepressant administration, are altered in the hippocampus of CN98 mice. These results suggest that calcineurin-dependent dephosphorylation plays an important role in the mechanisms of action of antidepressants, providing a new starting point for developing improved therapeutic treatments for depression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
144
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1470-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17207580-Animals, pubmed-meshheading:17207580-Antidepressive Agents, pubmed-meshheading:17207580-Antidepressive Agents, Tricyclic, pubmed-meshheading:17207580-Brain-Derived Neurotrophic Factor, pubmed-meshheading:17207580-Calcineurin, pubmed-meshheading:17207580-Depressive Disorder, pubmed-meshheading:17207580-Desipramine, pubmed-meshheading:17207580-Female, pubmed-meshheading:17207580-Fluoxetine, pubmed-meshheading:17207580-Hippocampus, pubmed-meshheading:17207580-Male, pubmed-meshheading:17207580-Mice, pubmed-meshheading:17207580-Mice, Inbred C57BL, pubmed-meshheading:17207580-Mice, Transgenic, pubmed-meshheading:17207580-Phosphorylation, pubmed-meshheading:17207580-Receptors, AMPA, pubmed-meshheading:17207580-Serotonin Uptake Inhibitors, pubmed-meshheading:17207580-Up-Regulation
pubmed:year
2007
pubmed:articleTitle
Calcineurin (protein phosphatase 2B) is involved in the mechanisms of action of antidepressants.
pubmed:affiliation
INSERM U-513, 8 rue de Général Sarrail, 94000 Créteil, France.
pubmed:publicationType
Journal Article