Journal
JOURNAL OF NEUROSCIENCE RESEARCH
Volume 73, Issue 1, Pages 1-9Publisher
WILEY
DOI: 10.1002/jnr.10634
Keywords
cholesterol; synaptogenesis; phospholipid; cdc42; synaptotagmin; cholesterol; mental retardation
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This study evaluated somatic and dendritic growth of neurons in the frontoparietal cortex of Igf1-/- brains. Pyramidal neuron density was increased by similar to25% (P = .005) and soma size reduced by similar to10% (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 similar to50% reduction in cortical CDC42 protein expression (P < .001) and an similar to10% 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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