title: Inducible nitric oxide synthase is involved in the modulation of depressive behaviors induced by unpredictable chronic mild stress.
abstract: BACKGROUND
  Experiences and inflammatory mediators are fundamental in the provocation of major depressive disorders (MDDs). We investigated the roles and mechanisms of inducible nitric oxide synthase (iNOS) in stress-induced depression.
  
  
  METHODS
  We used a depressive-like state mouse model induced by unpredictable chronic mild stress (UCMS). Depressive-like behaviors were evaluated after 4 weeks of UCMS, in the presence and absence of the iNOS inhibitor N-(3-(aminomethyl)benzyl)acetamidine (1400 W) compared with the control group. Immunohistochemistry was used to check the loss of Nissl bodies in cerebral cortex neurons. The levels of iNOS mRNA expression in the cortex and nitrites in the plasma were measured with real-time reverse transcription PCR (RT-PCR) and Griess reagent respectively.
  
  
  RESULTS
  Results showed that the 4-week UCMS significantly induced depressive-like behaviors, including decreased sucrose preference in a sucrose preference test, increased duration of immobility in a forced swim test, and decreased hole-searching time in a locomotor activity test. Meanwhile, in the locomotor activity test, UCMS had no effect on normal locomotor activities, such as resting time, active time and total travel distance. Furthermore, the levels of iNOS mRNA expression in the cortex and nitrites in the plasma of UCMS-exposed mice were significantly increased compared with that of the control group. Neurons of cerebral cortex in UCMS-exposed mice were shrunken with dark staining, together with loss of Nissl bodies. The above-mentioned stress-related depressive-like behaviors, increase of iNOS mRNA expression in the cortex and nitrites in the plasma, and neuron damage, could be abrogated remarkably by pretreating the mice with an iNOS inhibitor (1400 W). Moreover, neurons with abundant Nissl bodies were significantly increased in the 1400 W + UCMS group.
  
  
  CONCLUSIONS
  These results support the notion that stress-related NO (derived from iNOS) may contribute to depressive-like behaviors in a mouse model, potentially concurrent with neurodegenerative effects within the cerebral cortex.
authors.affiliation: Department of Nautical Medicine, Second Military Medical University, Shanghai, P R China.
authors.forename: Yun-Li
authors.initials: YL
authors.lastname: Peng
authors.forename: Yu-Ning
authors.initials: YN
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Jiang
authors.forename: Yun-Xia
authors.initials: YX
authors.lastname: Wang
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003865:Major Depressive Disorder / Q000201:enzymology* / Q000209:etiology / Q000523:psychology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D011237:Predictive Value of Tests; D013315:Stress, Psychological / Q000150:complications / Q000201:enzymology* / Q000523:psychology; D013997:Time Factors
chemical_list: D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse