Th1/Th2 immunity and cognitive deficit associated to chronic stress exposure. Involvement of nitric oxide production

MARÍA LAURA PALUMBO; MARÍA A ZORRILLA ZUBILETE; MIRIAM RUTH WALD; ANA MARÍA GENARO

Ciudad Autónoma de Buenos Aires

Congreso; XXXIX Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); 2007

Asociación Argentina de Farmacología Experimental (SAFE)

Stress and imbalance of Th1/Th2 immunity  has been implicated in psiquiatric disorders. Nitric oxide (NO) has been involved in many pathophysiological brain processes including hippocampal responses to stress. Here we investigated the effect of mild chronic stress (CMS) on learning and memory and NO participation in Th1-biased C57Bl/6 (C57) mice and Th2-biased Balb/c mice. We observed that CMS exposure induce an increase of  Th1- or Th2- type cytokine production  in C57 or Balb/c mice respectively. CMS-Balb/c mice showed a poor learning performance in open field test respect to control mice. In contrast, stress did not effect on learning performance in C57 mice. NO production by constitutive isoforms of NO synthase (NOS) was significantly disminished in the hippocampus of CMS-Balb/c mice but not in CMS-C57 mice respect to control. Moreover protein kinase C (PKC) activity was increased in CMS-Balb/c mice and significantly decreased in CMS-C57.  However, treatment of normal mice with general NOS inhibitor (L-NAME) induced a memory impairment in both strain of mice. These results suggest an important  role for NO and  the regulation of its production by PKC, in the cognitive deficit associated to chronic stress exposure. Moreover, Th1 response appears as a protective mechanism preventing NO decrease and memory impairment.