RT Journal Article
SR Electronic
T1 Bumetanide prevents brain trauma-induced depressive-like behavior
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 443739
DO 10.1101/443739
A1 Emmanuelle, Goubert
A1 Marc, Altvater
A1 Marie-Noelle, Rovira
A1 Ilgam, Khalilov
A1 Morgane, Mazzarino
A1 Anne, Sebastiani
A1 Michael, Schaefer
A1 Claudio, Rivera
A1 Christophe, Pellegrino
YR 2018
UL http://biorxiv.org/content/early/2018/10/16/443739.abstract
AB Brain trauma triggers a cascade of deleterious events leading to enhanced incidence of drug resistant epilepsies, depression and cognitive dysfunctions. The underlying mechanisms leading to these alterations are poorly understood and treatment that attenuates those sequels not available. Using controlled-cortical impact (CCI) as experimental model of brain trauma in adult mouse we found a strong suppressive effect of the sodium-potassium-chloride importer (NKCC1) specific antagonist bumetanide on appearance of depression-like behavior. We demonstrate that this alteration in behavior is associated with a block of CCI-induced decrease in parvalbumin-positive interneurons and impairment of post-traumatic secondary neurogenesis within the dentate gyrus of the hippocampus. The mechanism mediating the effect of bumetanide involves early transient changes in expression of chloride regulatory proteins and qualitative changes in GABA(A) mediated transmission after brain trauma. This work opens new perspectives in the early treatment of human post-traumatic induced depression. Our results strongly suggest that bumetanide might constitute an efficient prophylactic treatment to reduce neurological and psychiatric consequences of brain trauma.