Blockade of protein phosphatase 2B activity in the amygdala increases anxiety- and depression-like behaviors in mice
Authors: Marina R Picciotto
Yann S Mineur
Amine Bahi
Journal: Biological psychiatry (2009)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: organ transplant patients; calcineurin inhibitor; cyclosporin-A; mood disorders; amygdala
Affiliations: Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut, USA.

Abstract:  Background: Organ transplant patients receive chronic administration of the calcineurin inhibitor cyclosporin-A (CsA) and demonstrate increased incidence of mood disorders. Significant calcineurin expression can be observed with immunohistochemistry in the amygdala, a brain area important for behaviors related to mood disorders and anxiety. It is therefore important to determine whether chronic blockade of calcineurin might contribute to symptoms of anxiety and depression in these patients. Methods: Pharmacological CsA and viral-mediated gene transfer (adeno-associated viral expression of short hairpin RNA [AAV-shRNA]) approaches were used to inhibit calcineurin activity globally and selectively in the amygdala of the mouse brain to determine the role of calcineurin in behaviors related to depression and anxiety. Results: Systemic inhibition of calcineurin activity with CsA or local downregulation of calcineurin levels in the amygdala with AAV-delivered shRNAs targeting calcineurin A increased behavioral measures of anxiety in both the elevated plus maze and light/dark tests with no changes in locomotor activity. In the forced swim and tail suspension models of depression-like behavior, calcineurin blockade in the amygdala increased immobility similarly to manipulations that lead to a depression-like phenotype. Conclusions: Taken together, these data demonstrate that decreasing calcineurin activity in the amygdala increases anxiety- and depression-like behaviors. These studies suggest that chronic administration of CsA to organ transplant patients could have significant effects on anxiety and mood and that this should be recognized as a clinical consequence of treatment to prevent transplant rejection. 

Retracted: Yes

PubPeer comments:
 Figure 5A: Transcripts accumulation of ELIPs (RT-PCR analysis) in wild type plants maintained under low light (LL) or exposed to high light (HL) at room temperature (22 u00b0C) and to high light in the cold (4 u00b0C). Bands highlighted by boxes of same color appear to be much more similar than expected. Could the authors please post the uncropped scan of the original gels and take away any concerns? ![file] , 
 This is the outcome of the investigation by Editor-in Chief Dr. Motoaki Seki:  We have investigated the case as far as this is possible after more than 15 years. The corresponding author, Dr. Anna Paola Casazza, did her best, however, the original documents are no longer available, because the lab where the work was performed has been dismantled and Prof. Soave, head of the lab and last author of the paper, retired in 2012 and passed away in 2019. Dr. Anna Paola Casazza has expressed her confidence in the reliability of the results and told us that similar results have been published independently (Please see below), confirming their original observation. Huang et al. 2019 u201cThe Arabidopsis Transcriptome Responds Specifically and Dynamically to High Light Stressu201d CELL REPORTS 29: 4186 (doi: 10.1016 j.celrep.2019.11.051), who reproduced (Figure 1F) the expression pattern of Elip1 and Elip2 at high-light and room temperature; Nakamura et al. 2017 u201cCATchUP: A Web Database for Spatiotemporally Regulated Genesu201d PLANT AND CELL PHYSIOLOGY 58(1): e3(1u201318) (doi:10.1093 pcp pcw199), who developed a statistical method for the mining of spatiotemporally expressed genes using available large-scale RNA-Seq data. Authors confirmed that the experimental conditions (cold) in which Elip2 was specifically expressed in Arabidopsis was consistent between the previous studies (Casazza et al. 2005, PMB) and their study. We have no reason to doubt the validity of the data presented in the article. So, we close the case for Plant Molecular Biology now. ,