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Neuropeptide Trefoil Factor 3 Reverses Depressive-Like Behaviors by Activation of BDNF-ERK-CREB Signaling in Olfactory Bulbectomized Rats.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2015 Nov 30; Vol. 16 (12), pp. 28386-400. Date of Electronic Publication: 2015 Nov 30. - Publication Year :
- 2015
-
Abstract
- The trefoil factors (TFFs) are a family of three polypeptides, among which TFF1 and TFF3 are widely distributed in the central nervous system. Our previous study indicated that TFF3 was a potential rapid-onset antidepressant as it reversed the depressive-like behaviors induced by acute or chronic mild stress. In order to further identify the antidepressant-like effect of TFF3, we applied an olfactory bulbectomy (OB), a classic animal model of depression, in the present study. To elucidate the mechanism underlying the antidepressant-like activity of TFF3, we tested the role of brain-derived neurotrophic factor (BDNF)-extracellular signal-related kinase (ERK)-cyclic adenosine monophosphate response element binding protein (CREB) signaling in the hippocampus in the process. Chronic systemic administration of TFF3 (0.1 mg/kg, i.p.) for seven days not only produced a significant antidepressant-like efficacy in the OB paradigm, but also restored the expression of BDNF, pERK, and pCREB in the hippocampal CA3. Inhibition of BDNF or extracellular signal-related kinase (ERK) signaling in CA3 blocked the antidepressant-like activity of TFF3 in OB rats. Our findings further confirmed the therapeutic effect of TFF3 against depression and suggested that the normalization of the BDNF-ERK-CREB pathway was involved in the behavioral response of TFF3 for the treatment of depression.
- Subjects :
- Animals
Antidepressive Agents administration & dosage
Antidepressive Agents pharmacology
Depression drug therapy
Depression etiology
Disease Models, Animal
Hippocampus drug effects
Hippocampus metabolism
Male
Neuropeptides administration & dosage
Olfactory Bulb surgery
Phosphorylation
Rats
Receptor, trkB antagonists & inhibitors
Trefoil Factor-3
Behavior, Animal drug effects
Brain-Derived Neurotrophic Factor metabolism
Cyclic AMP Response Element-Binding Protein metabolism
Depression metabolism
Extracellular Signal-Regulated MAP Kinases metabolism
Neuropeptides pharmacology
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 16
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 26633367
- Full Text :
- https://doi.org/10.3390/ijms161226105