Different effect of chronic stress on learning and memory in BALB/c and C57BL/6 inbred mice: Involvement of hippocampal NO production and PKC activity.
Nitric oxide (NO) has been involved in many pathophysiological brain processes. Recently, we showed that neuronal nitric oxide synthase (nNOS)-mediated decrease in NO production is involved in memory impairment induced by chronic mild stress (CMS) in BALB/c mice. Two genetically different inbred murine strains, C57BL/6 and BALB/c, show distinct behavioral responses, neurodevelopmental and neurochemical parameters. Here, we perform a comparative study on 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 the open field and passive avoidance inhibitory tasks. Also, CMS induced a diminished NO production by nNOS, associated with an increment in gamma and zeta PKC isoenzymes in BALB/c mice. In C57BL/6 mice, CMS had no effect on NO production, but increased delta and decreased betaI PKC isoforms. In vivo administration of a NOS inhibitor induced behavioral alterations in both strains. These results suggest a differential effect of stress, with BALB/c being more vulnerable to stress than C57BL/6 mice. This effect could be related to a differential regulation of NOS and PKC isoenzymes, pointing to an important role of NO in learning and memory.
Palumbo
María Laura
ML
CEFYBO-CONICET, 1a Cát de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Zorrilla Zubilete
María Aurelia
MA
Cremaschi
Graciela Alicia
GA
Genaro
Ana María
AM
D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000201:enzymology; D007858:Learning; D008568:Memory / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D013315:Stress, Psychological / Q000503:physiopathology / Q000523:psychology*; D000099221:Protein Kinase C zeta
D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta; C496321:Nos1 protein, mouse; C087857:protein kinase C gamma