Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/61626

TitleLithium blocks stress-induced changes in depressive-like behavior and hippocampal cell fate: the role of glycogen-synthase-kinase-3beta
Author(s)Silva, Raian
Mesquita, A. R.
Bessa, João M.
Sousa, João Carlos
Sotiropoulos, I.
Leão, Pedro
Almeida, Osborne F. X.
Sousa, Nuno
KeywordsAdrenal Glands
Animals
Antimanic Agents
Behavior, Animal
Body Weight
Cell Proliferation
Cell Survival
Corticosterone
DNA-Binding Proteins
Depressive Disorder
Disease Models, Animal
Enzyme Inhibitors
Glycogen Synthase Kinase 3
Glycogen Synthase Kinase 3 beta
Hippocampus
Lithium Chloride
Male
Neuronal Plasticity
Neurons
Rats
Rats, Wistar
Stem Cells
Stress, Psychological
Synapsins
Synaptic Transmission
Transcription Factors
Up-Regulation
Chronic mild stress
Plasticity
B-cell-CLL/lymphoma 2
Bcl2-associated athanogene
Synapsin-I
Bcl -associated athanogene 2
Issue date27-Mar-2008
PublisherElsevier
JournalNeuroscience
Abstract(s)Mood disorders are the most common psychiatric disorders. Although the mechanisms implicated in the genesis of mood disorders are still unclear, stress is known to predispose to depression, and recently, studies have related hippocampal neurogenesis and apoptosis to depression. In the present study we first examined the balance between cell birth-death in the hippocampus and subventricular zone (SVZ) of pre-pubertal and adult rats subjected to chronic-mild-stress (CMS). CMS led to increased corticosterone secretion and induced depressive-like symptoms (assessed in the forced-swimming test); these endocrine and behavioral effects were paralleled by decreased hippocampal, but not SVZ, cell proliferation/differentiation and by increased apoptotic rate. In order to determine if lithium, a known mood stabilizer with antidepressant properties, could prevent the stress-induced events, we analyzed the same parameters in a group of rats treated with lithium during the stress exposure period (CMS+Li) and observed that the hormonal, behavioral and cell turnover effects of CMS were abrogated in these animals. Subsequently, to search for possible pathways through which CMS and lithium influence behavior, cell fate and synaptic plasticity, we analyzed the expression of glycogen-synthase-kinase-3beta (GSK-3beta), as well as some of its downstream targets (B-cell-CLL/lymphoma2-associated athanonege (BAG-1) and synapsin-I). CMS increased GSK-3beta and decreased synapsin-I and BAG-1 expression in the hippocampus. Interestingly, co-administration of lithium precluded the CMS-induced effects in GSK-3beta, synapsin-I and BAG-1 expression. Our observation that specific inhibition of this kinase with AR-A014418 blocked the effects of CMS in depressive-like behavior and in BAG-1 and synapsin-I expression confirmed the involvement of the GSK-3beta pathway in stress-induced effects. In summary, these results reveal that lithium, by regulating the activity of GSK-3beta, prevents the deleterious effects of stress on behavior and cellular functions.
TypeArticle
URIhttp://hdl.handle.net/1822/61626
DOI10.1016/j.neuroscience.2007.12.026
ISSN0306-4522
e-ISSN1873-7544
Peer-Reviewedyes
AccessRestricted access (Author)
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

Files in This Item:
File Description SizeFormat 
silva2008.pdf
  Restricted access
2,36 MBAdobe PDFView/Open

Partilhe no FacebookPartilhe no TwitterPartilhe no DeliciousPartilhe no LinkedInPartilhe no DiggAdicionar ao Google BookmarksPartilhe no MySpacePartilhe no Orkut
Exporte no formato BibTex mendeley Exporte no formato Endnote Adicione ao seu ORCID