Increased expression of insulin-like growth factor I augments the progressive phase of synaptogenesis without preventing synapse elimination in the hypoglossal nucleus.
The in vivo actions of insulin-like growth factor I (IGF-I) on synaptogenesis in the hypoglossal nucleus were investigated in transgenic mice that overexpress IGF-I in the brain postnatally and in normal nontransgenic littermate controls. In a previous study using these mice, we found that IGF-I increases the total volume of the hypoglossal nucleus by increasing the volume of neuropil rather than by increasing total neuron number; therefore, the progressive and regressive phases of synaptogenesis could be evaluated without the confounding effects of altered neuron number. The volume of the hypoglossal nucleus was significantly increased by 28% to 59% in transgenic mice after postnatal day (P) 7, whereas the total number of hypoglossal neurons did not differ significantly from controls. The numerical density of neurons was significantly decreased by 21% to 38% after P7, and the density of myelinated axons was significantly increased by 19%. Although the numerical density of synapses did not differ between groups at any age, the total number of synapses in transgenic mice was increased by 42% to 52% after P14. Total synapse number in controls increased from P7 (7.9 million) to peak values at P21 (36.0 million), followed by a significant decrease (33%) at P130 (24.2 million). In transgenic mice, total synapses increased from 8.2 million on P7 to 51.1 million on P21, followed by a significant decrease (28%) to 36.7 million at P130. Our results demonstrated that IGF-I can stimulate a persistent increase in the number of hypoglossal synapses, thereby augmenting the progressive phase of synaptogenesis without preventing synapse elimination during the regressive phase.
O'Kusky
John Robert
JR
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V5Z 1M9, Canada. jrokusky@interchange.ubc.ca
Ye
Ping
P
D'Ercole
A Joseph
AJ
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D007002:Hypoglossal Nerve / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008473:Median Eminence / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice / Q000254:growth & development / Q000378:metabolism*; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure
D007334:Insulin-Like Growth Factor I