使用胰岛素样生长因子治疗Rett综合征取得新进展


部分逆转MECP2突变小鼠的Rett综合征的症状
实验表明:胰岛素样生长因子1(IGF-1)能够延长MECP2突变小鼠的寿命,改善局部运动功能,改善呼吸,减少心率不齐,增加脑重量,增加脊柱密度和突触宽度,增加PSD-95,稳定皮质可塑性。该结果强烈显示胰岛素样生长因子1(IGF-1)可作为治疗Rett综合征和其它由于突触成熟延迟导致的中枢神经系统疾病。
类胰岛素一号增长因子

Rett Syndrome (RTT) is a severe form of X-linked mental retardation caused by mutations in the gene coding for methyl CpGbinding protein 2 (MECP2). Mice deficient in MeCP2 have a range
of physiological and neurological abnormalities that mimic the human syndrome. Here we show that systemic treatment of MeCP2 mutant mice with an active peptide fragment of Insulin-like
Growth Factor 1 (IGF-1) extends the life span of the mice, improves locomotor function, ameliorates breathing patterns, and reduces irregularity in heart rate. In addition, treatment with IGF-1 peptide increases brain weight of the mutant mice. Multiple measurements support the hypothesis that RTT results from a deficit in synaptic maturation in the brain: MeCP2 mutant mice have sparse dendritic spines and reduced PSD-95 in motor cortex pyramidal neurons, reduced synaptic amplitude in the same neurons, and protracted cortical plasticity in vivo. Treatment with IGF-1 peptide partially restores spine density and synaptic amplitude, increases PSD-95,
and stabilizes cortical plasticity to wild-type levels. Our results thus strongly suggest IGF-1 as a candidate for pharmacological treatment of RTT and potentially of other CNS disorders caused by delayed synapse maturation.

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