Dendritic stability in a model of adult-onset IGF-I deficiency.
OBJECTIVE
A significant decrease in plasma levels of insulin-like growth factor-I (IGF-I) is one of the most robust hallmarks of aging and may contribute to functional changes associated with senescence. This study examined the role of IGF-I in the maintenance of adult dendritic morphology.


METHODS
We utilized a model of the aging-related decrease in plasma IGF-I to examine whether such a decrease, in itself, leads to dendritic changes in the cerebral cortex. The dw/dw rat, originally of the Lewis strain, suffers from a spontaneous mutation in which growth hormone (GH) production is severely decreased. Since GH is responsible for the production of circulating IGF-I by the liver, these animals are deficient in plasma IGF-I. Homozygous dw/dw rats were administered porcine GH to sustain IGF-I levels during development and then GH injections were stopped as adults in order to examine the effects of adult-onset GH and IGF-I deficiency. Animals sacrificed after two or eight weeks of GH and IGF-I deficiency were compared to age-matched dw/dw animals that received GH both developmentally and throughout adulthood (GH/IGF-I replete). The dendritic arbors of pyramidal neurons in cingulate cortex were labeled by intracellular injection and reconstructed in three dimensions.


RESULTS
Comparing GH/IGF-I replete and deficient dw/dw rats, we found no differences in the apical or basal arbors of either layer two or layer five pyramidal neurons.


CONCLUSIONS
These findings indicate that a decrease in plasma levels of IGF-I is not sufficient in itself to produce dendritic changes like those seen in aging animals.
Grill
Joshua D
JD
Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Sonntag
William E
WE
Riddle
David R
DR
D000375:Aging / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002540:Cerebral Cortex / Q000473:pathology; D003712:Dendrites / Q000473:pathology*; D005260:Female; D013006:Growth Hormone / Q000172:deficiency / Q000494:pharmacology; D006720:Homozygote; D007334:Insulin-Like Growth Factor I / Q000172:deficiency*; D008297:Male; D051381:Rats; D011922:Rats, Mutant Strains
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone