Study Of The Nitric Oxide Synthase,Nitric Oxide And C-fos Gene Expression In Experimental Myasthenic Model Of Central Nervous System Dysfunction

Objective :The aim of present study is to explore the possible mechanism of central nervous system (CNS) dysfunction in myastheniagravis (MG).Method: The myasthenic model of CNS dysfunction was established byinjection of acetylcholine receptor antibody (AChRab) purified from MG sera into rat cerebral ventricular system.The NOS , NO level and its dynamic changes in brain , thymus and peripheral blood were tested. Then we use immunohistochemical method to investigate the c-fos gene expression in rat CNS neurons.These results were then compared with normal controls that injected with normal human IgG. Results: Model rats presented the symptoms and signs which imitated experimental autoimmune myasthenia gravis (EAMG).Level of NOS and NO in brain ,thymus and peripheral blood was significantly increased compared with control group (P<0.01). Dynamic observation: All of the observated values started to increase at the end of 1st week.Level of NOS and NO in brain reached the peak; Level of NOS and No in thymus and peripheral blood reached the peak at the end of 2nd week.All values began to descend at the end of 3st week,but still remained higher than control group.From the whole viewpoint, the level of the NOS and NO are paralleled with the animal's symptom and the time of injection with AChRab. Correlation analysis showed:NOS was related with NO in brain. Both NOS and NO wera also postively correlation with those in thymus-n-98and blood respectively.Correlation coefficient were 0.7155, 0.6806N 0.7891 respectively, P<0.01. The strong Fos positive neuron was found in the cerebral cortex, basis nuclei, hypothalamus ,hippocampus, brain stem motor nuclei,auditory nucleus,cerebellum cortex, lateral hypothalamic region,septal area,gyrus cinguli,mamillary body,substantia nigra,red nucleus,corpus striatum et al 3 hour after three times intracerebroventricular administration of IgG(AChAb).These expression reached the peak at the end of 4-5 hours and significantly extinguished except a few areas like the cerebral cortex, hypothalamus, hippocampus after 12 hours.Conclusin: The results indicate that cerebroventricular administration of AChRab can cause CNS dysfunction of rats.Level of the NOS ,NO significantly increased in the brain and peripheral blood in model of CNS dysfunction in MG, and the level is paralleled with the animal's symptom.All these indicating that NOS ,NO play an important role in causing CNS dysfunction. The expression of c-fos gene may be related to induce the change of neurotransmitter or cytokine.Then the change may lead to CNS dysfunction of rat.