Chronic stress induces different effect on learning and memory in BALB/c and C57BL/6 mice associated to different regulation of NO production by PKC activity.

PALUMBO ML; ZORRILLA ZUBILETE M; CREMASCHI GA; GENARO AM

Tandil, Buenos Aires

Congreso; XL Reunión Anual de la Asociación Argentina de Farmacología Experimental; 2008

Asociación Argentina de Farmacología Experimental

Stress and imbalance of Th1/Th2 immunity has been implicated in psiquiatric disorders. Two genetically different inbred murine strains, C57BL/6 and BALB/c, show different behavioral responses, neurodevelopmental and neurochemical parameters Nitric oxide (NO) has been involved in many pathophysiological brain processes including hippocampal responses to stress. Here, we perform a comparative study on chronic mild stress (CMS) effects upon learning and memory in both strains, analyzing the role of NO production and its regulation by protein kinase C (PKC). Stressed BALB/c, but not C57BL/6 mice, showed a poor learning performance in both open field and passive avoidance inhibitory task. Control C57BL/6 mice showed a higher basal NOS activity than control BALB/c. In CMS BALB/c but not C57BL/6 mice a significative decrease of NOS activity was observed respect to control. PKC inhibition induced appositive effects on NOS activity in stressed mice respect to control depending on the strain studied. Western blot analysis of PKC isoforms revealed that CMS exposition induced an increased in æ and ã PKC isoforms in BALB/c mice. On the other hand, CMS C57BL/6 mice showed an increase in ä and a decrease in â1 PKC isoforms. These results suggest a differential effect of stress, being BALB/c more vulnerable to stress than C57BL/6 mice. This effect could be related to a differential regulation of NOS and PKC isoenzymes.