Research Article

Insulin-like growth factor 1 is essential for normal dendritic growth†

  1. Clara M. Cheng1,
  2. Ronald F. Mervis2,
  3. Shui-Lin Niu3,
  4. Norman Salem Jr.3,
  5. Lee A. Witters4,
  6. Victor Tseng1,
  7. Rickey Reinhardt1,
  8. Carolyn A. Bondy1,*

Article first published online: 8 MAY 2003

DOI: 10.1002/jnr.10634

Issue

Journal of Neuroscience Research

Journal of Neuroscience Research

Volume 73, Issue 1, pages 1–9, 1 July 2003

Additional Information

How to Cite

Cheng, C. M., Mervis, R. F., Niu, S.-L., Salem, N., Witters, L. A., Tseng, V., Reinhardt, R. and Bondy, C. A. (2003), Insulin-like growth factor 1 is essential for normal dendritic growth. J. Neurosci. Res., 73: 1–9. doi: 10.1002/jnr.10634

Author Information

  1. 1

    Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland

  2. 2

    NeuroStructure Research Laboratories, Columbus, Ohio

  3. 3

    Laboratory of Membrane Biophysics and Biochemistry, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland

  4. 4

    Department of Medicine and Biochemistry, Dartmouth Medical School, Hanover, New Hampshire

*Bldg. 10/10N262, 10 Center Dr., NIH, Bethesda, MD 20892

  1. †

    This article is a US Government work and, as such, is in the public domain in the United States of America.

Publication History

  1. Issue published online: 13 JUN 2003
  2. Article first published online: 8 MAY 2003
  3. Manuscript Accepted: 7 MAR 2003
  4. Manuscript Revised: 27 FEB 2003
  5. Manuscript Received: 13 FEB 2003

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Keywords:

  • cholesterol;
  • synaptogenesis;
  • phospholipid;
  • cdc42;
  • synaptotagmin;
  • cholesterol;
  • mental retardation

Abstract

This study evaluated somatic and dendritic growth of neurons in the frontoparietal cortex of Igf1–/– brains. Pyramidal neuron density was increased by ∼25% (P = .005) and soma size reduced by ∼10% (P < .001). Golgi staining revealed that cortical layer II–III neurons exhibited a significant reduction in dendritic length and complexity in Igf1 null mice. Dendritic spine density and presumably synaptic contacts were reduced by 16% (P = .002). Similar findings were obtained for cortical layer V and piriform cortex pyramids. Supporting a reduction in synapses, synaptotagmin levels were reduced by 30% (P < .02) in the Igf1 null brain. Investigation of factors critically involved in dendritic growth and synaptogenesis showed an ∼50% reduction in cortical CDC42 protein expression (P < .001) and an ∼10% reduction in brain cholesterol levels (P < .01) in Igf1 null mice. Evidence is presented that Igf1 deletion causes disruptions in lipid and microtubule metabolism, leading to impaired neuronal somatic and dendritic growth. Published 2003 Wiley-Liss, Inc.

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