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

• Published in: Journal of neuroscience research Vol. 73; no. 1; pp. 1 - 9
• Main Authors: Cheng, Clara M., Mervis, Ronald F., Niu, Shui-Lin, Salem Jr, Norman, Witters, Lee A., Tseng, Victor, Reinhardt, Rickey, Bondy, Carolyn A.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2003
• Subjects: Animals; cdc42; Cell Count; Cell Division; Cell Size - physiology; cholesterol; Cholesterol - analysis; Dendrites - chemistry; Dendrites - physiology; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - metabolism; mental retardation; Mice; Mice, Mutant Strains; Neurites - chemistry; Neurites - physiology; phospholipid; Pyramidal Cells - chemistry; Pyramidal Cells - cytology; Pyramidal Cells - ultrastructure; Silver Staining; Synapses - physiology; synaptogenesis; synaptotagmin
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.10634

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.