title: Increased expression of insulin-like growth factor I augments the progressive phase of synaptogenesis without preventing synapse elimination in the hypoglossal nucleus.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V5Z 1M9, Canada. jrokusky@interchange.ubc.ca
authors.forename: John Robert
authors.initials: JR
authors.lastname: O'Kusky
authors.forename: Ping
authors.initials: P
authors.lastname: Ye
authors.forename: A Joseph
authors.initials: AJ
authors.lastname: D'Ercole
mesh_terms: 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
chemical_list: D007334:Insulin-Like Growth Factor I