Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay
Open accessAbstract
BACKGROUND: 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. FINDINGS: 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. CONCLUSIONS: 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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
IGF1 is considered an emerging treatment for ASD in animal and cellular models.
“Insulin like growth factor 1 (IGF1) is considered an emerging treatment for ASD in animal and cellular models in ASD [133–136].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [136]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism
Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y. S., Mele, A., Fraser, C. E., Stone, E. F., Chen, C., Fak, J. J., Chi, S. W., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.013 · Cited by 2,072 · see citing works
Advances in autism genetics: on the threshold of a new neurobiology
Abrahams, B. S., & Geschwind, D. H. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2346 · Cited by 1,866 · see citing works
Marchetto, M. C. N., Carromeu, C., Acab, A., Yu, D., Yeo, G. W., Mu, Y., Chen, G., Gage, F. H., & Muotri, A. R. (2010) · Cell · doi:10.1016/j.cell.2010.10.016 · Cited by 1,329 · see citing works
Contribution of SHANK3 Mutations to Autism Spectrum Disorder
Moessner, R., Marshall, C. R., Sutcliffe, J. S., Skaug, J., Pinto, D., Vincent, J., Zwaigenbaum, L., Fernandez, B., Roberts, W., Szatmari, P., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/522590 · Cited by 681 · see citing works
Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice
Tropea, D., Giacometti, E., Wilson, N. R., Beard, C., McCurry, C., Fu, D. D., Flannery, R., Jaenisch, R., & Sur, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812394106 · Cited by 593 · see citing works
Bozdagi, O., Sakurai, T., Papapetrou, D., Wang, X., Dickstein, D. L., Takahashi, N., Kajiwara, Y., Yang, M., Katz, A. M., Scattoni, M. L., et al. (2010) · Molecular Autism · doi:10.1186/2040-2392-1-15 · Cited by 584 · see citing works
Self-citationSynaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3
Wang, X., McCoy, P. A., Rodriguiz, R. M., Pan, Y., Je, H. S., Roberts, A. C., Kim, C. J., Berrios, J., Colvin, J. S., Bousquet-Moore, D., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr212 · Cited by 537 · see citing works
Yang, M., Bozdagi, O., Scattoni, M. L., Wöhr, M., Roullet, F. I., Katz, A. M., Abrams, D. N., Kalikhman, D., Simon, H., Woldeyohannes, L., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.6107-11.2012 · Cited by 369 · see citing works
Self-citationO'Kusky, J. R., Ye, P., & D'Ercole, A. J. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-22-08435.2000 · Cited by 358 · see citing works
Hamdan, F. F., Gauthier, J., Araki, Y., Lin, D.-T., Yoshizawa, Y., Higashi, K., Park, A.-R., Spiegelman, D., Dobrzeniecka, S., Piton, A., et al. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.02.001 · Cited by 349 · see citing works
Boeckers, T. M., Bockmann, J., Kreutz, M. R., & Gundelfinger, E. D. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00931.x · Cited by 349 · see citing works
Nishijima, T., Piriz, J., Duflot, S., Fernandez, A. M., Gaitán, G., Gómez‐Pinedo, U., García‐Verdugo, J. M., Leroy, F., Soya, H., Núñez, Á., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.007 · Cited by 335 · see citing works
Protein interactome reveals converging molecular pathways among autism disorders
Sakai, Y., Shaw, C. A., Dawson, B. C., Dugas, D. V., Al-Mohtaseb, Z., Hill, D. E., & Zoghbi, H. Y. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002166 · Cited by 226 · see citing works
The Role of Neuronal Complexes in Human X-Linked Brain Diseases
Laumonnier, F., Cuthbert, P. C., & Grant, S. G. N. (2007) · The American Journal of Human Genetics · doi:10.1086/511441 · Cited by 121 · see citing works
Differential Effects of Aging and Insulin-like Growth Factor-1 on Synapses in CA1 of Rat Hippocampus
Shi, L., Linville, M. C., Tucker, E. W., Sonntag, W. E., & Brunso‐Bechtold, J. K. (2004) · Cerebral Cortex · doi:10.1093/cercor/bhh158 · Cited by 95 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Advancing the understanding of autism disease mechanisms through genetics
de la Torre-Ubieta, L., Won, H., Stein, J. L., & Geschwind, D. H. (2016) · Nature Medicine · doi:10.1038/nm.4071 · Cited by 827 · see citing works
Excess of rare, inherited truncating mutations in autism
Krumm, N., Turner, T. N., Baker, C., Vives, L., Mohajeri, K., Witherspoon, K., Raja, A., Coe, B. P., Stessman, H. A., He, Z.-X., et al. (2015) · Nature Genetics · doi:10.1038/ng.3303 · Cited by 587 · see citing works
Cerebral plasticity: windows of opportunity in the developing brain
Ismail, F. Y., Fatemi, A., & Johnston, M. V. (2017) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2016.07.007 · Cited by 572 · see citing works
Excitation/Inhibition Imbalance in Animal Models of Autism Spectrum Disorders
Lee, E., Lee, J., & Kim, E. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.05.011 · Cited by 468 · see citing works
Genes, circuits, and precision therapies for autism and related neurodevelopmental disorders
Sahin, M., & Sur, M. (2015) · Science · doi:10.1126/science.aab3897 · Cited by 295 · see citing works
An Update on Psychopharmacological Treatment of Autism Spectrum Disorder
Aishworiya, R., Valica, T., Hagerman, R., & Restrepo, B. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01183-1 · Cited by 233 · see citing works
Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat
Harony-Nicolas, H., Kay, M., Hoffmann, J. D., Klein, M. E., Bozdagi-Gunal, O., Riad, M., Daskalakis, N. P., Sonar, S., Castillo, P. E., Hof, P. R., et al. (2017) · eLife · doi:10.7554/elife.18904 · Cited by 168 · see citing works
Self-citationCLK2 inhibition ameliorates autistic features associated with SHANK3 deficiency
Bidinosti, M., Botta, P., Krüttner, S., Proenca, C. C., Stoehr, N., Bernhard, M., Fruh, I., Mueller, M., Bonenfant, D., Voshol, H., et al. (2016) · Science · doi:10.1126/science.aad5487 · Cited by 151 · see citing works
Dysregulation of the IGF‐I/PI3K/AKT/mTOR signaling pathway in autism spectrum disorders
Chen, J., Alberts, I., & Li, X. (2014) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2014.03.006 · Cited by 151 · see citing works
Protective role of IGF-1 and GLP-1 signaling activation in neurological dysfunctions
Bhalla, S., Mehan, S., Khan, A., & Rehman, M. U. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104896 · Cited by 108 · see citing works
Truncating mutations in RBM12 are associated with psychosis
Steinberg, S., Gudmundsdottir, S., Sveinbjornsson, G., Suvisaari, J., Paunio, T., Torniainen-Holm, M., Frigge, M. L., Jonsdottir, G. A., Huttenlocher, J., Arnarsdottir, S., et al. (2017) · Nature Genetics · doi:10.1038/ng.3894 · Cited by 70 · see citing works
Linker, S. B., Mendes, A. P. D., & Marchetto, M. C. (2020) · Molecular Autism · doi:10.1186/s13229-020-00359-w · Cited by 31 · see citing works
New therapeutic options for autism spectrum disorder: experimental evidences
Peñagarikano, O. (2015) · Experimental Neurobiology · doi:10.5607/en.2015.24.4.301 · Cited by 24 · see citing works
- Authors
- Bozdagi, O., Tavassoli, T., & Buxbaum, J. D.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Buxbaum, Joseph D
- Venue
- Molecular Autism
- Published
- 2013-04-27
- Volume
- 4
- Issue
- 1
- Pages
- 9-9
- ISSN
- 2040-2392 (ISSN-L)
- PMC
- PMC3649942
- OpenAlex
- W2135432133
- Cited by
- 176
- References
- 15
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 7 · 2023: 11 · 2022: 19 · 2021: 22 · 2020: 9 · 2019: 6 · 2018: 10 · 2017: 18 · 2016: 26 · 2015: 17 · 2014: 15 · 2013: 1
- FWCI
- 13.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Autism (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Simons Foundation
- National Institute of Mental Health (R01MH093725)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- insulin-like growth factor I, SHANK3, autism spectrum disorder, developmental delay, 22q13 deletion syndrome, Phelan-McDermid syndrome, haploinsufficiency, long-term potentiation, synaptic function, motor impairment, Rett syndrome, glutamate signaling, therapeutic rescue
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
