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Augmentation of the NO-cGMP cascade induces anxiogenic-like effect in mice

100%

Volke V., Wegener G., Vasar E.

Journal of Physiology and Pharmacology

2003

tom 54

nr 4

Several studies have reported the anxiolytic-like effects of various nitric oxide synthase inhibitors in distinct animal models. However, in the context of anxiety, the possible involvement of cyclic GMP, believed to be one of the main targets of NO, remains obscure. Cyclic GMP is degraded by the specific phosphodiesterases in the brain. Therefore, we studied the effect of the selective phosphodiesterase type 5 inhibitor sildenafil in the mouse elevated plus-maze test of anxiety and in the open field test of locomotion. We found that sildenafil (0.05-10 mg/kg i.p.) alone did not affect the behavior of animals in the plus-maze or open field tests, but the anxiogenic beta-carboline DMCM given in a subconvulsive dose (2 mg/kg i.p.) decreased the time spent on open arms in the elevated plus-maze. Treatment with the NO precursor L-arginine (200 mg/kg i.p.) did not modify the behavior of animals in the plus-maze, however, when sildenafil (1 mg/kg i.p.) was administered in combination with L-arginine (200 mg/kg i.p.), both the time spent on the open arms and the percentage of open arm visits were significantly decreased. We conclude that augmentation of the NO-cGMP cascade induces anxiogenic-like effect in mice.

Alpha-synuclein A30P point-mutation generates age-dependent nigrostriatal deficiency in mice

64%

Plaas M., Karis A., Innos J., Rebane E., Baekelandt V., Vaarmann A., Luuk H., Vasar E., Koks S.

Journal of Physiology and Pharmacology

2008

tom 59

nr 2

Lewy bodies are mainly composed of alpha-synuclein (SNCA) and specific mutations in SNCA gene are related to familial forms of Parkinson's disease (PD). The purpose of our study was to generate a mouse line with A30P knock-in point mutation in SNCA gene and to test if a single point-mutation is able to turn otherwise normal SNCA into a toxic form. The behavioral profile of SNCA A30P mice was followed for 16 months. Generally, these mice are healthy and viable without any obvious abnormalities. Starting from the age of 13 months mice developed a significant deficit in motor performance tests related to nigrostriatal function (ink-test and beam walk). In other tests (motility boxes, rotarod) mice continuously performed normally. Moreover, SNCA A30P mice expressed the altered sensitivity to VMAT2 inhibitor reserpine, possibly reflecting a functional deficiency of dopamine. Indeed, mice at 15 months of age had significantly reduced levels of dopamine and its major metabolite DOPAC in the striatum, and reduced levels of dopamine in the mesolimbic system. The present study confirms that SNCA plays an important role in the development of PD and an insertion of a single point mutation is sufficient to generate age-related decline in specific motor performance. The generated mouse line has a potential to become a model for PD with comparable time course and phenotype.

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

2 Vasar E.

1 Baekelandt V.

1 Innos J.

1 Karis A.

1 Koks S.

1 Luuk H.

1 Plaas M.

1 Rebane E.

1 Vaarmann A.

1 Volke V.

1 Wegener G.

1 2008

1 2003

Wyniki wyszukiwania

Augmentation of the NO-cGMP cascade induces anxiogenic-like effect in mice

Alpha-synuclein A30P point-mutation generates age-dependent nigrostriatal deficiency in mice