Maternal Immune Activation with H1N1 or Toxoplasma gondii Antigens Induces Behavioral Impairments Associated with Mood Disorders in Rodents.

ABSTRACT

INTRODUCTION: Epidemiological studies revealed that maternal exposure to influenza A (H1N1) and Toxoplasma gondii (T. gondii) infection during pregnancy may increase the risk for mood disorders of the offspring. However, the impact of maternal infections in different stages of neural development and the nature of antigens remain to be elucidated. OBJECTIVE: This study investigated behavioral impairments induced by maternal immune activation (MIA) due to H1N1 or T. gondii infection during preborn neurodevelopment. METHODS: Maternal infection with influenza or toxoplasma was mimicked by administration of influenza vaccine antigens or suspension of soluble T. gondii antigen (STAg) in pregnant Balb/c mice at E6 or E16. Adult male offspring were evaluated for anxiety-like and depressive-like behavior in elevated plus maze (EPM) and forced swimming test (FST). RESULTS: In FST, immobility time at E6 and E16 increased when the mothers were treated with both antigen solutions. There was increased immobility in the pups whose mothers were treated with STAg at E16. MIA with influenza antigens reduced the exploration of the open arms of EPM for the pups whose progenitors received treatment at E6 and E16. The animals at E6 exhibited a greater number of stretch-attend postures compared with the saline group. STAg at E6 reduced the time of exploration in the open arms and increased the number of stretch-attend postures compared with the saline group. CONCLUSION: These results suggest that immunological responses to H1N1 or T. gondii during pregnancy may impact differently the susceptibility of adult offspring to mood disorder.