Psychological dominant stressor modification to an animal model of depression with chronic unpredictable mild stress.

Background and Aim: Chronic unpredictable mild stress (CUMS) is a protocol widely used to create an animal model of depression with food deprivation, water deprivation, and physical-dominant stressors as routine procedures. However, human depression mainly involves psychological stressors and does not always involve a lack of food and water; thus, CUMS procedures should be modified accordingly. Therefore, this study aimed to create an animal model of depression, mainly focusing on a psychologically dominant stressor without food and water deprivation. Materials and Methods: The CUMS and control groups, respectively, received CUMS modification (psychologically dominant stressors without food and water deprivation) for 21 days. A 24-h sucrose preference test (SPT) was used to assess the successful creation of an animal model of depression. Daily food intake measurements, weekly weight monitoring, and weight gain calculations were performed. Either an independent sample t-test or the Mann-Whitney test was used. Results: Of the 42 rats included, 39 completed the study. Chronic unpredictable mild stress procedures for 21 days significantly reduced the SPT (p < 0.05), mean body weight (p < 0.05), and weekly weight gain (p < 0.05) in the CUMS group compared to the control group. However, the weekly average food intake did not statistically differ between the two groups. Conclusion: Psychological dominant CUMS modification to an animal model of depression resulted in lower SPT, body weight, and weekly weight gain in the CUMS group than in the control group.

Isoniazid (INH) treatment of INH-resistant Mycobacterium tuberculosis inhibits infected macrophage to produce TNF-alpha.

Macrophages undergo apoptosis after infected by Mycobacterium tuber- culosis (M.tb), which is regulated by tumor necrosis factor alpha (TNF-alpha) and has a direct correlation with killing of intracellular bacilli. In order to clarify the role of isoniazid (INH) in the modulation of macrophages apoptosis and intracellular bacilli replication, we performed the following studies using an INH-resistant clinical M.tb isolate (INHres). Macrophages derived from peripheral blood were infected with INHres and treated or not treated with INH. Apoptosis was measured using an Ag-capture ELISA for histone and fragmented DNA. Production of TNF-alpha by INHres infected was assayed using ELISA and viability of intracellular M.tb was determined using bacterial culture of macrophage lysates on Lowenstein-Jensen (LJ) medium. INH pre-treatment to INHres reduced macrophages apoptosis, production of TNF-alpha and intracellular INHres viability. This study indicated that INH affected TNF-alpha release resulting in reduction of the extent macrophages apoptosis and of intracellular INH-resistant M.tb viability.