Antidepressant actions of lateral habenula deep brain stimulation differentially correlate with CaMKII/GSK3/AMPK signaling locally and in the infralimbic cortex

Kim, Yesul, Morath, Brooke, Hu, Chunling, Byrne, Linda K, Sutor, Shari L., Frye, Mark A. and Tye, Susannah J. 2016, Antidepressant actions of lateral habenula deep brain stimulation differentially correlate with CaMKII/GSK3/AMPK signaling locally and in the infralimbic cortex, Behavioural brain research, vol. 306, pp. 170-177, doi: 10.1016/j.bbr.2016.02.039.

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Title Antidepressant actions of lateral habenula deep brain stimulation differentially correlate with CaMKII/GSK3/AMPK signaling locally and in the infralimbic cortex
Author(s) Kim, Yesul
Morath, Brooke
Hu, Chunling
Byrne, Linda KORCID iD for Byrne, Linda K orcid.org/0000-0001-9055-0046
Sutor, Shari L.
Frye, Mark A.
Tye, Susannah J.
Journal name Behavioural brain research
Volume number 306
Start page 170
End page 177
Total pages 25
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2016
ISSN 1872-7549
Keyword(s) AMPK
CaMKII
Deep brain stimulation
GSK3
Lateral habenula
Treatment resistant depression
Science & Technology
Life Sciences & Biomedicine
Behavioral Sciences
Neurosciences
Neurosciences & Neurology
TREATMENT-RESISTANT DEPRESSION
VENTRAL TEGMENTAL AREA
SUBCALLOSAL CINGULATE GYRUS
ACTIVATED PROTEIN-KINASE
DORSAL RAPHE NUCLEUS
FORCED SWIM TEST
MOOD DISORDERS
SYNAPTIC POTENTIATION
METABOLIC-CHANGES
TREATED RATS
Summary High frequency deep brain stimulation (DBS) of the lateral habenula (LHb) reduces symptoms of depression in severely treatment-resistant individuals. Despite the observed therapeutic effects, the molecular underpinnings of DBS are poorly understood. This study investigated the efficacy of high frequency LHb DBS (130Hz; 200μA; 90μs) in an animal model of tricyclic antidepressant resistance. Further, we reported DBS mediated changes in Ca(2+)/calmodulin-dependent protein kinase (CaMKIIα/β), glycogen synthase kinase 3 (GSK3α/β) and AMP-activated protein kinase (AMPK) both locally and in the infralimbic cortex (IL). Protein expressions were then correlated to immobility time during the forced swim test (FST). Antidepressant actions were quantified via FST. Treatment groups comprised of animals treated with adrenocorticotropic hormone alone (ACTH; 100μg/day, 14days, n=7), ACTH with active DBS (n=7), sham DBS (n=8), surgery only (n=8) or control (n=8). Active DBS significantly reduced immobility in ACTH-treated animals (p<0.05). For this group, western blot results demonstrated phosphorylation status of LHb CaMKIIα/β and GSK3α/β significantly correlated to immobility time in the FST. Concurrently, we observed phosphorylation status of CaMKIIα/β, GSK3α/β, and AMPK in the IL to be negatively correlated with antidepressant actions of DBS. These findings suggest that activity dependent phosphorylation of CaMKIIα/β, and GSK3α/β in the LHb together with the downregulation of CaMKIIα/β, GSK3α/β, and AMPK in the IL, contribute to the antidepressant actions of DBS.
Language eng
DOI 10.1016/j.bbr.2016.02.039
Field of Research 170106 Health, Clinical and Counselling Psychology
Socio Economic Objective 920410 Mental Health
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Elsevier B.V.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30082407

Document type: Journal Article
Collection: School of Psychology
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