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Intracerebroventricular Administration of Streptozotocin as an Experimental Approach to Depression: Evidence for the Involvement of Proinflammatory Cytokines and Indoleamine-2,3-Dioxygenase
- Source :
- Neurotoxicity Research. 31:464-477
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- There is a lack of information about the molecular events underlying the depressive-like effect of an intracerebroventricular injection of streptozotocin (ICV-STZ) in mice. Elevated activity of the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase (IDO) has been proposed to mediate depression in inflammatory disorders. In this study, we report that ICV-STZ activates IDO in the hippocampus of mice and culminates in depressive-like behaviors, measured by an increased duration in immobility time in the forced swimming test and decreased total time of grooming in the splash test. Indirect blockade of IDO activation with the cytokine inhibitor minocycline prevents the development of depressive-like behaviors and attenuates STZ-induced upregulation of proinflammatory cytokines in the hippocampus. Minocycline abrogates the increase in tryptophan and kynurenine levels as well as prevents serotonin dysfunction in the hippocampus of STZ-injected mice. These results suggest that hippocampal IDO activation in STZ-associated depressive-like behavior is mediated by proinflammatory cytokine-dependent mechanisms. Our study not only extends the evidence that IDO has a critical role in mediating inflammation-induced depression but also supports the notion that neuroinflammation and the kynurenine pathway are important targets of novel therapeutic drugs for depression. In addition, our study provides new insights into the neurobiological mechanisms underlying ICV-STZ and indicates that this model could be employed in the preclinical research of depression.
- Subjects :
- Blood Glucose
Male
Serotonin
medicine.medical_specialty
Kynurenine pathway
medicine.medical_treatment
Minocycline
Toxicology
Hippocampus
Streptozocin
Proinflammatory cytokine
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Animals
Indoleamine-Pyrrole 2,3,-Dioxygenase
Indoleamine 2,3-dioxygenase
Kynurenine
Neuroinflammation
Depression
General Neuroscience
Tryptophan
Immobility Response, Tonic
Hydroxyindoleacetic Acid
Grooming
030227 psychiatry
Disease Models, Animal
Infusions, Intraventricular
Cytokine
Endocrinology
chemistry
Cytokines
Psychology
030217 neurology & neurosurgery
Behavioural despair test
Subjects
Details
- ISSN :
- 14763524 and 10298428
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- Neurotoxicity Research
- Accession number :
- edsair.doi.dedup.....d22888a4d9745fb4729786363cfe07df