Advance on insulin-like growth factor-1 in autism spectrum disorders

doi:10.11852/zgetbjzz2018-1095

Abstract

Abstract: The diagnosis of autism spectrum disorder (ASD) is mainly dependent on behavioral symptoms,and most children could not receive accurate diagnosis until 4 years old when the impairment of social interaction presents typically and the best period of intervention has been missed. It is worth noting that scientists have made a lot of theoretical and practical research on the pathological mechanism and drug target of ASD. And more and more studies have shown that the biomarker,insulin-like growth factor-1 (IGF-1),plays an important role in the development and progression in ASD. This review will summarize the role of IGF-1 in ASD in order to elucidate that IGF-1 is expected to be a biomarker of early diagnosis and early prevention of ASD,and to explore the application of IGF-1.

Key words: autism spectrum disorder, insulin-like growth factor-1, SHANK3 gene, Engrailed2 gene, MECP2 protein

摘要： 孤独症谱系障碍(ASD)确诊主要采用现有行为学症状诊断方法,大多数ASD儿童在到了4岁左右才得到准确诊断,而此时患儿的社交障碍已经十分明显,错失了干预治疗的最佳时期。值得注意的是,国内外学者对ASD的病理机制和药物靶标进行了大量研究,越来越多结果表明胰岛素样生长因子-1(IGF-1)在ASD的发生发展中占据重要地位。本文针对IGF-1在ASD中的作用进行综述,目的是为阐明IGF-1有望成为ASD早期诊断、早期治疗的生物标志物及探讨IGF-1在ASD中的应用前景。

关键词: 孤独症谱系障碍, 胰岛素样生长因子-1, SHANK3基因, Engrailed2基因, MECP2蛋白

CLC Number:

R749.94

HONG Xiao-wen, CHEN Yan-hui. Advance on insulin-like growth factor-1 in autism spectrum disorders[J]. journal1, 2019, 27(1): 56-58.

洪晓文综述, 陈燕惠审校. 胰岛素样生长因子1在孤独症谱系障碍中的研究进展[J]. 中国儿童保健杂志, 2019, 27(1): 56-58.

References

[1] Geschwind DH,State MW.Gene hunting in autism spectrum disorder:on the path to precision medicine[J].Lancet Neurol,2015,14:1109-1120.
[2] Llorens-Martín M,Torres-Alemán I,Trejo JL.Mechanisms mediating brain plasticity:IGF1 and adult hippocampal neurogenesis[J].Neuroscientist,2009,15:134-148.
[3] Hellström A,Ley D,Hansen-Pupp I,et al. Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development[J].Acta Pediatr,2016,105:576-586.
[4] Park H,Poo MM.Neurotrophin regulation of neural circuit development and function[J].Nat Rev Neurosci,2013,14:7-23.
[5] Nieto-Este'vez V,Defterali C,Vicario-Abejón C. IGF-I:a key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain[J].Front Neurosci,2016,10:52.
[6] Zikopoulos B,Barbas H.Changes in prefrontal axons may disrupt the network in autism[J].J Neurosci,2010,30(44):14595-14609.
[7] Riikonen R,Makkonen I,Vanhala R,et al.Cerebrospinal fluid insulin-like growth factors IGF-1 and IGF-2 in infantile autism[J].Dev Med Child Neurol,2006,48(9):751-755.
[8] Dinleyici EC,Tekin N,Colak O,et al.Cord blood IGF-1 and IGFBP-3 levels in asphyxiated term newborns[J].Neuro Endocrinol Lett,2006,27(6):745-747.
[9] ElaineY,Hsiao P,Patterson H.Maternal infection and immune involvement in autism[J].Trends Mol Med,2011,17(7):389-394.
[10] Steinman G,Mankuta D.Insulin-like growth factor and the etiology of autism[J].Med Hypotheses,2013,80(4):475-480.
[11] Carlson S,Madathi S,Sama D,et al.Conditional overexpression of insulin-like growth factor-1 enhances hippocampal neurogenesis and restores immature neuron dendritic processes after traumatic brain injury[J].J Neuropathol Exp Neurol,2014,73:734-746.
[12] Sakai Y,Shaw CA,Dawson BC,et al.Protein interactome reveals converging molecular pathways among autism disorders[J].Sci Transl Med,2011,3(86):86ra49.
[13] Martha RH.SHANK3,the synapse,and autism[J].N Engl J Med,2011,365(2):173-175.
[14] Bozdagi O,Tavassoli T,Buxbaum JD.Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay[J].Molecular Autism,2013,4(1):9.
[15] Benayed R,Choi J,Matteson PG,et al.Autism-associated haplotype affects the regulation of the homeobox gene,ENGRAILED 2[J].Biol Psychiatry,2009,66(10):911-917.
[16] Rossman IT,Lin LL,Morgan KM,et al.Engrailed2 modulates cerebellar granule neuron precursor proliferation,differentiation and insulin-like growth factor 1 signaling during postnatal development[J].Molecular Autism,2014,5(1):9.
[17] Provenzano G,Clementi E,Genovesi S,et al.GH dysfunction in engrailed-2 knockout mice,a model for autism spectrum disorders[J].Front Pediatr,2014,2:92.
[18] Guy J,Cheval H,Selfridge J,et al.The role of MECP2 in the brain[J].Annu Rev Cell Dev Biol,2011,27:631-652.
[19] Blackman MP,Djukic B,Nelson SB,et al.A critical and cell-autonomous role for MeCP2 in synaptic scaling-up[J].J Neurosci,2012,32(29):13529-13536.
[20] Tropea D,Mortimer N,Molinos I,et al.Expression of nuclear methyl-CpG binding protein 2 (Mecp2) is dependent on neuronal stimulation and application of insulin-like growth factor1[J].Neurosci Lett,2016,621:111-116.
[21] Castro J,Garcia RI,Kwok S,et al.Functional recovery with recombinant human IGF1 treatment in a mouse model of Rett Syndrome[J].Proc Natl Acad Sci USA,2016,111(27):9941-9946.
[22] Purkayastha P,Malapati A,Yogeeswari P,et al. A review on GABA/glutamate pathway for therapeutic intervention of ASD and ADHD[J].Curr Med Chem,2015,22(15):1850-1859.
[23] Tang X,Kim J,Zhou L,et al.KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome[J].PNAS,2016,113(3):751-756.
[24] Riikonen R.Insulin-like growth factors in the pathogenesis of neurological diseases in children[J].Int J Mol Sci,2017,18(10):2056.
[25] A pilot treatment study of insulin-like growth factor-1(IGF-1) in autism spectrum disorder[EB/OL].NCT01970345.https://www.clinicaltrials.gov/ct2/show/NCT01970345?term=IGF-1&cond=ASD&rank=1
[26] Khwaja OS,Ho E,Barnes KV,et al.Safety,pharmacokinetics,and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome[J].Proc Natl Acad Sci USA.,2014,111(12):4596-4601.
[27] Pini G,Scusa MF,Benincasa A,et al.Repeated insulin-like growth factor 1 treatment in a patient with rett syndrome:a single case study[J].Front Paediatry,2014,2:52.
[28] Vahdatpour C,Dyer AH,Tropea D.Insulin-like growth factor 1 and related compounds in the treatment of childhood-onset Neurodevelopmental disorders[J].Front Neurosci,2016,10:450.
[29] Kolevzon A,Bush L,Wang AT,et al.A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome[J].Molecular Autism,2014,5:54.
[30] Marchetto MC,Belinson H,Tian Y,et al.Altered proliferation and networks in neural cells derived from idiopathic autistic individuals[J].Mol Psychiatry,2016,doi:10.1038/mp.2016.95
[31] Chen J,Alberts I,Li X. Dysregulation of the IGF-I/PI3K/AKT/ mTOR signaling pathway in autism spectrum disorders[J].Int J Dev Neurosci,2014,35:35-41.
[32] Tropea D,Mortimer N,Bellini S,et al.Expression of nuclear Methyl-CpG binding protein 2 (Mecp2) is dependent on neuronal stimulation and application of insulin-like growth factor 1[J].Neurosci Lett,2016,16(621):111-116.