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Increased expression of insulin‐like growth factor I augments the progressive phase of synaptogenesis without preventing synapse elimination in the hypoglossal nucleus
Author(s) -
O'Kusky John Robert,
Ye Ping,
D'Ercole A. Joseph
Publication year - 2003
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.10794
Subject(s) - synaptogenesis , hypoglossal nucleus , biology , insulin like growth factor , endocrinology , medicine , synapse , neuron , neuropil , transgene , nucleus , neuroscience , growth factor , central nervous system , receptor , biochemistry , gene
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. J. Comp. Neurol. 464:382–391, 2003. © 2003 Wiley‐Liss, Inc.