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Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice.

Publication ,  Journal Article
Pardo, M; Cheng, Y; Velmeshev, D; Magistri, M; Eldar-Finkelman, H; Martinez, A; Faghihi, MA; Jope, RS; Beurel, E
Published in: JCI Insight
March 23, 2017

Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve genetically impaired learning and memory. In mice modeling the intellectual deficiency of Fragile X syndrome, intranasally administered siRNA targeting glycogen synthase kinase-3β (GSK3β), histone deacetylase-1 (HDAC1), HDAC2, or HDAC3 diminished cognitive impairments. In WT mice, intranasally administered brain-derived neurotrophic factor (BDNF) siRNA or HDAC4 siRNA impaired learning and memory, which was partially due to reduced insulin-like growth factor-2 (IGF2) levels because the BDNF siRNA- or HDAC4 siRNA-induced cognitive impairments were ameliorated by intranasal IGF2 administration. In Fmr1-/- mice, hippocampal IGF2 was deficient, and learning and memory impairments were ameliorated by IGF2 intranasal administration. Therefore intranasal siRNA administration is an effective means to identify mechanisms regulating cognition and to modulate therapeutic targets.

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Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

March 23, 2017

Volume

2

Issue

6

Start / End Page

e91782

Location

United States

Related Subject Headings

  • RNA, Small Interfering
  • Mice, Knockout
  • Mice
  • Insulin-Like Growth Factor II
  • Histone Deacetylases
  • Glycogen Synthase Kinase 3 beta
  • Fragile X Syndrome
  • Fragile X Mental Retardation Protein
  • Cognition Disorders
  • Animals
 

Citation

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Pardo, M., Cheng, Y., Velmeshev, D., Magistri, M., Eldar-Finkelman, H., Martinez, A., … Beurel, E. (2017). Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice. JCI Insight, 2(6), e91782. https://doi.org/10.1172/jci.insight.91782
Pardo, Marta, Yuyan Cheng, Dmitry Velmeshev, Marco Magistri, Hagit Eldar-Finkelman, Ana Martinez, Mohammad A. Faghihi, Richard S. Jope, and Eleonore Beurel. “Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice.JCI Insight 2, no. 6 (March 23, 2017): e91782. https://doi.org/10.1172/jci.insight.91782.
Pardo M, Cheng Y, Velmeshev D, Magistri M, Eldar-Finkelman H, Martinez A, et al. Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice. JCI Insight. 2017 Mar 23;2(6):e91782.
Pardo, Marta, et al. “Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice.JCI Insight, vol. 2, no. 6, Mar. 2017, p. e91782. Pubmed, doi:10.1172/jci.insight.91782.
Pardo M, Cheng Y, Velmeshev D, Magistri M, Eldar-Finkelman H, Martinez A, Faghihi MA, Jope RS, Beurel E. Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice. JCI Insight. 2017 Mar 23;2(6):e91782.

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

March 23, 2017

Volume

2

Issue

6

Start / End Page

e91782

Location

United States

Related Subject Headings

  • RNA, Small Interfering
  • Mice, Knockout
  • Mice
  • Insulin-Like Growth Factor II
  • Histone Deacetylases
  • Glycogen Synthase Kinase 3 beta
  • Fragile X Syndrome
  • Fragile X Mental Retardation Protein
  • Cognition Disorders
  • Animals