Changes in acetylcholinesterase in experimental autoimmune myasthenia gravis and in response to treatment with a specific antisense

摘要: Controlled regulation of synaptic nicotinic acetylcholine receptors (AChRs) and acetylcholinesterase (AChE), together with maintenance a dynamic balance between them, is requirement for proper function cholinergic synapses. In the present study we assessed whether pathological changes in AChR perturb this balance, such can be corrected. We studied influence loss, caused by experimental autoimmune myasthenia gravis (EAMG), on muscle AChE, as well reciprocal effect an antisense targeted towards AChE both at neuromuscular synapse. The extensor digitorum longus (EDL) muscles EAMG Lewis rats were isolated, levels isoform compositions examined. Although healthy similar, marked observed composition. Healthy EDL contained globular (G(1,2) , G(4) ) asymmetric (primarily A(12) isoforms. G(1,2) -AChE was significantly reduced muscles, whereas - remained unchanged. Treatment EN101 resulted decreased total recovery reduction -AChE. AChE/AChR ratios determined junctions (NMJ). decrease that occurred disease progressed dramatic increase ratio, significant normal after treatment. This improvement primarily due to increased content. Our findings emphasise tight connection myasthenic NMJ, importance ratio maintaining required balance.