Abstract：
: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.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Crozatier C,Farley S,Mansuy IM,Dumas S,Giros B,Tzavara ETdoi
10.1016/j.neuroscience.2006.11.030subject
Has Abstractpub_date
2007-02-23 00:00:00pages
1470-6issue
4eissn
0306-4522issn
1873-7544pii
S0306-4522(06)01636-8journal_volume
144pub_type
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