title: Neotrofin reverses the effects of chronic unpredictable mild stress on behavior via regulating BDNF, PSD-95 and synaptophysin expression in rat.
abstract: Depression is one of the most common neuropsychiatric disorders and has been associated with a wide range of neuronal structural changes in brain regions. Neotrofin, a neurotrophin agonist, has been demonstrated to exhibit neuroprotection in various in vivo and in vitro studies. The present study aimed to investigate the neuroprotective and ameliorating effects of neotrofin treatment in a rat model of chronic unpredictable mild stress (CUMS) induced depression. The results showed that CUMS was effective in producing depression-like behavior in rats as indicated by decreased responses in the sucrose preference test, and locomotor activity in the open-field test. Moreover, the expression of brain-derived neurotrophic factor (BDNF), PSD-95 and synaptophysin were decreased in the amygdala of CUMS rats. Chronic administration of neotrofin (60mg/kg, i.p., 5 weeks) significantly ameliorated all these behavioral and biochemical alterations associated with CUMS induced depression, which demonstrated that the expression changes of BDNF, PSD-95 and synaptophysin were correlated with the depression-like behaviors of CUMS rats. Taken together, the results of the present study highlight that neotrofin exhibits neuroprotective and antidepressant-like effects against CUMS induced depression, and suggest a possible mechanism for this protection via changes in synaptic plasticity within the amygdala. These findings reveal the therapeutic potential of neotrofin for use in clinical trials in the treatment of neuronal deterioration in depression.
authors.affiliation: Department of Physiology, Shandong University, School of Medicine, Wenhuaxilu Road, Jinan, Shandong Province 250012, PR China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Luo
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Nannan
authors.initials: N
authors.lastname: Ning
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Shu Yan
authors.initials: SY
authors.lastname: Yu
mesh_terms: D062365:Aminobenzoates / Q000494:pharmacology*; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D002908:Chronic Disease; D003627:Data Interpretation, Statistical; D000076122:Disks Large Homolog 4 Protein; D005518:Food Preferences / Q000187:drug effects; D007042:Hypoxanthines / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D018696:Neuroprotective Agents; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000523:psychology*; D013395:Sucrose; D016708:Synaptophysin / Q000096:biosynthesis*
chemical_list: D062365:Aminobenzoates; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D007042:Hypoxanthines; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D016708:Synaptophysin; C086241:4-((3-(1,6-dihyro-6-oxo-9H-purin-9-yl)-1-oxopropyl)amino)benzoic acid; D013395:Sucrose
keywords: AD; ANOVA; Alzheimer's disease; Amygdala; BDNF; CUMS; Chronic unpredictable mild stress; Depression; NGF; NT-3; NT-4; Neotrofin; PSD-95; analysis of variance; brain derived neurotrophic factor; chronic unpredictable mild stress; nerve growth factor; neurotrophin-3; neurotrophin-4; postsynaptic density protein 95