NDLI: Fluoxetine Signature on Hippocampal MAPK Signalling in Sex-Dependent Manner

Content Provider	Springer Nature Link
Author	Mitic, Milos Lukic, Iva Bozovic, Natalija Djordjevic, Jelena Adzic, Miroslav
Copyright Year	2014
Abstract	A growing body of evidence indicates that mitogen-activated protein kinase (MAPK) participates in various stress-induced responses and is considered to be one of the pathophysiological mechanisms in depression. Surprisingly, the effect of antidepressants on MAPKs is almost unexplored, particularly from the perspective of sexes. The present study investigates the cytoplasm-nuclear distribution of MAPK family, c-Jun N-terminal kinases (JNKs) 1, 2 and 3; extracellular signal-regulated kinases (ERKs) 1 and 2; and p38 kinases, as well as their phosphoisoforms in the hippocampus of chronically stressed female and male rats and upon chronic fluoxetine treatment. Additionally, we analysed crosstalk between MAPK signalling and depressive-like behaviour which correlated with brain-derived neurotrophic factor (BDNF) expression. Our results emphasize a gender-specific and compartment-dependent response of MAPKs to stress and fluoxetine. In females, stress decreased pp38 and pJNK and induced cytosolic retention of pERKs which reduced all nuclear pMAPKs. These changes correlated with altered BDNF expression and behaviour. Similarly, in males, stress decreased pp38 but promoted nuclear translocation of pJNKs and pERKs. These stress alterations of pMAPKs in males were not associated with BDNF expression and depressive-like behaviour. Fluoxetine treatment in stressed females upregulated whole pMAPK signalling particularly those in nucleus which was followed with BDNF expression and normalization of behaviour. In stressed males, fluoxetine affected only cytosolic pJNKs, while nuclear pMAPK signalling and BDNF expression were unaffected even though fluoxetine normalized behaviour. Overall, our results suggest existence of gender-specific mechanism of fluoxetine on nuclear pMAPK/BDNF signalling and depressive-like behaviour and reinforce the antidepressant dogma that females and males respond differently to certain antidepressants.
Starting Page	335
Ending Page	346
Page Count	12
File Format	PDF
ISSN	08958696
Journal	Journal of Molecular Neuroscience
Volume Number	55
Issue Number	2
e-ISSN	15591166
Language	English
Publisher	Springer US
Publisher Date	2014-05-21
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Fluoxetine MAPK signalling Gender Chronic stress Hippocampus Neurosciences Neurochemistry Cell Biology Proteomics Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Cellular and Molecular Neuroscience

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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