Potential Involvement of Impaired BKCa Channel Function in Sensory Defensiveness and Some Behavioral Disturbances Induced by Unfamiliar Environment in a Mouse Model of Fragile X Syndrome.

Maria Isabel Carreno-Munoz, Fabienne Martins, Maria Carmen Medrano, Elisabetta Aloisi, Susanna Pietropaolo, Corentin Dechaud, Enejda Subashi, Guillaume Bony, Melanie Ginger, Abdelmalik Moujahid, Andreas Frick, Xavier Leinekugel
Neuropsychopharmacology. 2017-07-19; 43(3): 492-502
DOI: 10.1038/npp.2017.149

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1. Neuropsychopharmacology. 2018 Feb;43(3):492-502. doi: 10.1038/npp.2017.149. Epub
2017 Jul 19.

Potential Involvement of Impaired BKCa Channel Function in Sensory Defensiveness
and Some Behavioral Disturbances Induced by Unfamiliar Environment in a Mouse
Model of Fragile X Syndrome.

Carreno-Munoz MI(1)(2)(3), Martins F(1)(2), Medrano MC(1)(2), Aloisi E(1)(2),
Pietropaolo S(4)(5), Dechaud C(1)(2), Subashi E(1)(2), Bony G(1)(2), Ginger
M(1)(2), Moujahid A(3), Frick A(1)(2), Leinekugel X(1)(2).

Author information:
(1)INSERM, Neurocentre Magendie, U1215, Bordeaux, France.
(2)University of Bordeaux, Neurocentre Magendie, U1215, Bordeaux, France.
(3)University of the Basque Country (UPV/EHU), Donostia, Spain.
(4)University of Bordeaux, INCIA, Pessac, France.
(5)CNRS, INCIA, UMR 5287, Pessac, France.

In fragile X syndrome (FXS), sensory hypersensitivity and impaired habituation is
thought to result in attention overload and various behavioral abnormalities in
reaction to the excessive and remanent salience of environment features that
would normally be ignored. This phenomenon, termed sensory defensiveness, has
been proposed as the potential cause of hyperactivity, hyperarousal, and negative
reactions to changes in routine that are often deleterious for FXS patients.
However, the lack of tools for manipulating sensory hypersensitivity has not
allowed the experimental testing required to evaluate the relevance of this
hypothesis. Recent work has shown that BMS-204352, a BKCa channel agonist, was
efficient to reverse cortical hyperexcitability and related sensory
hypersensitivity in the Fmr1-KO mouse model of FXS. In the present study, we
report that exposing Fmr1-KO mice to novel or unfamiliar environments resulted in
multiple behavioral perturbations, such as hyperactivity, impaired nest building
and excessive grooming of the back. Reversing sensory hypersensitivity with the
BKCa channel agonist BMS-204352 prevented these behavioral abnormalities in
Fmr1-KO mice. These results are in support of the sensory defensiveness
hypothesis, and confirm BKCa as a potentially relevant molecular target for the
development of drug medication against FXS/ASD.

DOI: 10.1038/npp.2017.149
PMCID: PMC5770751 [Available on 2019-02-01]
PMID: 28722023


Auteurs Bordeaux Neurocampus