Sequence of abnormal dendritic spine development in primary somatosensory cortex of a mouse model of the fragile X mental retardation syndrome - PubMed

Affiliations

• PMID: 15880753
• DOI: 10.1002/ajmg.a.30709

Comparative Study

Sequence of abnormal dendritic spine development in primary somatosensory cortex of a mouse model of the fragile X mental retardation syndrome

Roberto Galvez et al. Am J Med Genet A. 2005.

Abstract

Anatomical analyses of occipital and temporal cortex of patients with fragile X mental retardation syndrome (FXS) and in a mouse model of the syndrome (FraX mice) compared to controls have suggested that the fragile X mental retardation protein (FMRP) is important for normal spine structural maturation and pruning. However, a recent analysis of spine properties in somatosensory cortex of young FraX mice has suggested that this region may not exhibit spine abnormalities. While spine abnormalities were present 1 week after birth in somatosensory cortex, by 4 weeks almost all spine abnormalities had disappeared, suggesting that adult spine abnormalities observed in other cortical regions may not persist post-developmentally in somatosensory cortex. To resolve this discrepancy we examined spine properties in somatosensory cortex of young (day 25) and adult (day 73-76) FraX compared to wild-type (WT) mice. Spine properties in young FraX and WT mice did not consistently differ from each other, consistent with the recent analysis of developing somatosensory cortex. However, adult FraX mice exhibited increased spine density, longer spines, more spines with an immature-appearing structure, fewer shorter spines, and fewer spines with a mature structure, a pattern consistent with prior analyses from other adult cortical brain regions in humans and mice. These findings (1) support the previous report of the absence of major spine abnormalities in the fourth postnatal week, (2) demonstrate normal spine development in WT mice, (3) demonstrate abnormal spine development after the fourth postnatal week in FraX mice, and (4) demonstrate spine abnormalities in somatosensory cortex of adult FraX compared to adult WT mice. In doing so, these findings resolve a potential conflict in the literature and more thoroughly describe the role of FMRP in spine development.

Similar articles

• Somatosensory cortical barrel dendritic abnormalities in a mouse model of the fragile X mental retardation syndrome.

  Galvez R, Gopal AR, Greenough WT. Galvez R, et al. Brain Res. 2003 May 2;971(1):83-9. doi: 10.1016/s0006-8993(03)02363-1. Brain Res. 2003. PMID: 12691840

• Dendritic spine abnormalities in the occipital cortex of C57BL/6 Fmr1 knockout mice.

  McKinney BC, Grossman AW, Elisseou NM, Greenough WT. McKinney BC, et al. Am J Med Genet B Neuropsychiatr Genet. 2005 Jul 5;136B(1):98-102. doi: 10.1002/ajmg.b.30183. Am J Med Genet B Neuropsychiatr Genet. 2005. PMID: 15892134

• Fragile X-like behaviors and abnormal cortical dendritic spines in cytoplasmic FMR1-interacting protein 2-mutant mice.

  Han K, Chen H, Gennarino VA, Richman R, Lu HC, Zoghbi HY. Han K, et al. Hum Mol Genet. 2015 Apr 1;24(7):1813-23. doi: 10.1093/hmg/ddu595. Epub 2014 Nov 28. Hum Mol Genet. 2015. PMID: 25432536 Free PMC article.

• Dendritic spine structural anomalies in fragile-X mental retardation syndrome.

  Irwin SA, Galvez R, Greenough WT. Irwin SA, et al. Cereb Cortex. 2000 Oct;10(10):1038-44. doi: 10.1093/cercor/10.10.1038. Cereb Cortex. 2000. PMID: 11007554 Review.

• The trouble with spines in fragile X syndrome: density, maturity and plasticity.

  He CX, Portera-Cailliau C. He CX, et al. Neuroscience. 2013 Oct 22;251:120-8. doi: 10.1016/j.neuroscience.2012.03.049. Epub 2012 Apr 20. Neuroscience. 2013. PMID: 22522472 Free PMC article. Review.

Cited by

• Rescue of dendritic spine phenotype in Fmr1 KO mice with the mGluR5 antagonist AFQ056/Mavoglurant.

  Pop AS, Levenga J, de Esch CE, Buijsen RA, Nieuwenhuizen IM, Li T, Isaacs A, Gasparini F, Oostra BA, Willemsen R. Pop AS, et al. Psychopharmacology (Berl). 2014 Mar;231(6):1227-35. doi: 10.1007/s00213-012-2947-y. Epub 2012 Dec 21. Psychopharmacology (Berl). 2014. PMID: 23254376

• Modeling fragile X syndrome in the Fmr1 knockout mouse.

  Kazdoba TM, Leach PT, Silverman JL, Crawley JN. Kazdoba TM, et al. Intractable Rare Dis Res. 2014 Nov;3(4):118-33. doi: 10.5582/irdr.2014.01024. Intractable Rare Dis Res. 2014. PMID: 25606362 Free PMC article. Review.

• Fragile X syndrome and model organisms: identifying potential routes of therapeutic intervention.

  Bhogal B, Jongens TA. Bhogal B, et al. Dis Model Mech. 2010 Nov-Dec;3(11-12):693-700. doi: 10.1242/dmm.002006. Epub 2010 Aug 3. Dis Model Mech. 2010. PMID: 20682752 Free PMC article. Review.

• Physiological and anatomical studies of associative learning: Convergence with learning studies of W.T. Greenough.

  Galvez R, Nicholson DA, Disterhoft JF. Galvez R, et al. Dev Psychobiol. 2011 Jul;53(5):489-504. doi: 10.1002/dev.20554. Dev Psychobiol. 2011. PMID: 21678397 Free PMC article. Review.

• Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach us.

  Santos AR, Kanellopoulos AK, Bagni C. Santos AR, et al. Learn Mem. 2014 Sep 16;21(10):543-55. doi: 10.1101/lm.035956.114. Print 2014 Oct. Learn Mem. 2014. PMID: 25227249 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Wiley

• Medical

  • MedlinePlus Health Information