Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay.
Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay.
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DOI：
10.1186/2040-2392-4-9
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发表时间：
2013-04-27
期刊：
影响因子：
6.2
通讯作者：
Buxbaum JD
中科院分区：
文献类型：
--
作者：
Bozdagi O;Tavassoli T;Buxbaum JD
由于半合子基因缺失（称为22q13缺失综合征或费伦 - 麦克德米德综合征）或基因突变导致的SHANK3单倍体不足，约占自闭症谱系障碍（ASD）和/或发育迟缓病例的0.5%，并且有证据表明SHANK3和谷氨酸信号异常在ASD及相关病症中具有更广泛的作用。因此，逆转SHANK3单倍体不足缺陷的治疗方法可能对ASD和发育迟缓具有广泛的益处。
我们观察到，在两周时间内每日腹腔注射人胰岛素样生长因子1（IGF - 1），可逆转我们之前在Shank3缺陷小鼠中所报道的海马α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸（AMPA）信号传导、长时程增强（LTP）以及运动表现方面的缺陷。使用一种IGF - 1肽衍生物也观察到了积极效果。
我们在一种ASD和发育迟缓的小鼠模型中观察到IGF - 1具有显著的有益作用。在雷特综合征的小鼠和人类神经元模型中的研究也显示IGF - 1具有益处，这增加了这种化合物可能对ASD及相关病症具有广泛益处的可能性，即使分子病因不同。鉴于在因原发性IGF - 1缺乏而身材矮小的儿童中IGF - 1有大量的安全性数据，IGF - 1是在SHANK3缺乏和ASD中进行对照临床试验的一个有吸引力的候选药物。
Haploinsufficiency of SHANK3, due to either hemizygous gene deletion (termed 22q13 deletion syndrome or Phelan-McDermid syndrome) or to gene mutation, accounts for about 0.5% of the cases of autism spectrum disorder (ASD) and/or developmental delay, and there is evidence for a wider role for SHANK3 and glutamate signaling abnormalities in ASD and related conditions. Therapeutic approaches that reverse deficits in SHANK3-haploinsufficiency may therefore be broadly beneficial in ASD and in developmental delay. We observed that daily intraperitoneal injections of human insulin-like growth factor 1 (IGF-1) over a 2-week period reversed deficits in hippocampal α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) signaling, long-term potentiation (LTP), and motor performance that we had previously reported in Shank3-deficient mice. Positive effects were observed with an IGF-1 peptide derivative as well. We observed significant beneficial effects of IGF-1 in a mouse model of ASD and of developmental delay. Studies in mouse and human neuronal models of Rett syndrome also show benefits with IGF-1, raising the possibility that this compound may have benefits broadly in ASD and related conditions, even with differing molecular etiology. Given the extensive safety data for IGF-1 in children with short stature due to primary IGF-1 deficiency, IGF-1 is an attractive candidate for controlled clinical trials in SHANK3-deficiency and in ASD.
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影响因子：
6.2
作者：
Bozdagi O;Sakurai T;Papapetrou D;Wang X;Dickstein DL;Takahashi N;Kajiwara Y;Yang M;Katz AM;Scattoni ML;Harris MJ;Saxena R;Silverman JL;Crawley JN;Zhou Q;Hof PR;Buxbaum JD
通讯作者：
Buxbaum JD
DOI：
10.1523/jneurosci.6107-11.2012
发表时间：
2012-05-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Yang M;Bozdagi O;Scattoni ML;Wöhr M;Roullet FI;Katz AM;Abrams DN;Kalikhman D;Simon H;Woldeyohannes L;Zhang JY;Harris MJ;Saxena R;Silverman JL;Buxbaum JD;Crawley JN
通讯作者：
Crawley JN
影响因子：
16.2
作者：
Nishijima, Takeshi;Piriz, Joaquin;Torres-Aleman, Ignacio
通讯作者：
Torres-Aleman, Ignacio
影响因子：
64.5
作者：
Darnell JC;Van Driesche SJ;Zhang C;Hung KY;Mele A;Fraser CE;Stone EF;Chen C;Fak JJ;Chi SW;Licatalosi DD;Richter JD;Darnell RB
通讯作者：
Darnell RB
影响因子：
3.7
作者：
Shi, L;Linville, MC;Brunso-Bechtold, JK
通讯作者：
Brunso-Bechtold, JK