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Flotillin-1 interacts with the serotonin transporter and modulates chronic corticosterone response.


ABSTRACT: Aberrant serotonergic neurotransmission in the brain is considered at the core of the pathophysiological mechanisms involved in neuropsychiatric disorders. Gene by environment interactions contribute to the development of depression and involve modulation of the availability and functional activity of the serotonin transporter (SERT). Using behavioral and in vivo electrophysiological approaches together with biochemical, molecular-biological and molecular imaging tools we establish Flotillin-1 (Flot1) as a novel protein interacting with SERT and demonstrate its involvement in the response to chronic corticosterone (CORT) treatment. We show that genetic Flot1 depletion augments chronic CORT-induced behavioral despair and describe concomitant alterations in the expression of SERT, activity of serotonergic neurons and alterations of the glucocorticoid receptor transport machinery. Hence, we propose a role for Flot1 as modulatory factor for the depressogenic consequences of chronic CORT exposure and suggest Flotillin-1-dependent regulation of SERT expression and activity of serotonergic neurotransmission at the core of the molecular mechanisms involved.

SUBMITTER: Reisinger SN 

PROVIDER: S-EPMC6392109 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Flotillin-1 interacts with the serotonin transporter and modulates chronic corticosterone response.

Reisinger S N SN   Kong E E   Molz B B   Humberg T T   Sideromenos S S   Cicvaric A A   Steinkellner T T   Yang J-W JW   Cabatic M M   Monje F J FJ   Sitte H H HH   Nichols B J BJ   Pollak D D DD  

Genes, brain, and behavior 20180520 2


Aberrant serotonergic neurotransmission in the brain is considered at the core of the pathophysiological mechanisms involved in neuropsychiatric disorders. Gene by environment interactions contribute to the development of depression and involve modulation of the availability and functional activity of the serotonin transporter (SERT). Using behavioral and in vivo electrophysiological approaches together with biochemical, molecular-biological and molecular imaging tools we establish Flotillin-1 (  ...[more]

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