Insulin-like growth factor 1 is essential for normal dendritic growth.
This study evaluated somatic and dendritic growth of neurons in the frontoparietal cortex of Igf1-/- brains. Pyramidal neuron density was increased by approximately 25% (P =.005) and soma size reduced by approximately 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 approximately 50% reduction in cortical CDC42 protein expression (P <.001) and an approximately 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.
Cheng
Clara M
CM
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Mervis
Ronald F
RF
Niu
Shui-Lin
SL
Salem
Norman
N
Witters
Lee A
LA
Tseng
Victor
V
Reinhardt
Rickey
R
Bondy
Carolyn A
CA
D000818:Animals; D002452:Cell Count; D002455:Cell Division; D048429:Cell Size / Q000502:physiology; D002784:Cholesterol / Q000032:analysis; D003712:Dendrites / Q000737:chemistry / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D016501:Neurites / Q000737:chemistry / Q000502:physiology; D017966:Pyramidal Cells / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D016622:Silver Staining; D013569:Synapses / Q000502:physiology
D007334:Insulin-Like Growth Factor I; D002784:Cholesterol