caa a22 4500 477038425 CHVBK 20180405111310.0 cr unu---uuuuu 170330e19961201xx s 000 0 eng 10.1007/BF02740625 doi (NATIONALLICENCE)springer-10.1007/BF02740625 The role of the insulin-like growth factors in the central nervous system [Elektronische Daten] [A. D'Ercole, Ping Ye, Ali Calikoglu, Gabriel Gutierrez-Ospina] Increasing evidence strongly supports a role for insulin-like growth factor-I (IGF-I) in central nervous system (CNS) development. IGF-I, IGF-II, the type IIGF receptor (the cell surface tyrosine kinase receptor that mediates IGF signals), and some IGF binding proteins (IGFBPs; secreted proteins that modulate IGF actions) are expressed in many regions of the CNS beginningin utero. The expression pattern of IGF system proteins during brain growth suggests highly regulated and developmentally timed IGF actions on specific neural cell populations. IGF-I expression is predominantly in neurons and, in many brain regions, peaks in a fashion temporally coincident with periods in development when neuron progenitor proliferation and/or neuritic outgrowth occurs. In contrast, IGF-II expression is confined mainly to cells of mesenchymal and neural crest origin. While expression of type I IGF receptors appears ubiquitous, that of IGFBPs is characterized by regional and developmental specificity, and often occurs coordinately with peaks of IGF expression. In vitro IGF-I has been shown to stimulate the proliferation of neuron progenitors and/or the survival of neurons and oligodendrocytes, and in some cultured neurons, to stimulate function. Transgenic (Tg) mice that overexpress IGF-I in the brain exhibit postnatal brain overgrowth without anatomic abnormality (20-85% increases in weight, depending on the magnitude of expression). In contrast, Tg mice that exhibit ectopic brain expression of IGFBP-1, an inhibitor of IGF action when present in molar excess, manifest postnatal brain growth retardation, and mice with ablated IGF-I gene expression, accomplished by homologous recombination, have brains that are 60% of normal size as adults. Taken together, these in vivo studies indicate that IGF-I can influence the development of most, if not all, brain regions, and suggest that the cerebral cortex and cerebellum are especially sensitive to IGF-I actions. IGF-I's growth-promoting in vivo actions result from its capacity to increase neuron number, at least in certain populations, and from its potent stimulation of myelination. These IGF-I actions, taken together with its neuroprotective effects following CNS and peripheral nerve injury, suggest that it may be of therapeutic benefit in a wide variety of disorders affecting the nervous system. Humana Press Inc, 1996 Insulin-like growth factors nationallicence insulin-like growth factor receptors nationallicence insulin-like growth factor binding proteins nationallicence brain nationallicence transgenic mice nationallicence BBB : blood-brain barrier nationallicence CNS : central nervous system nationallicence E : embryonic day nationallicence EGF : epidermal growth factor nationallicence EAE : experimental autoimmune encephalomyelitis nationallicence FGF : fibroblast growth factor nationallicence GH : growth hormone nationallicence ISHH : in situ hybridization histochemistry nationallicence IRS : insulin receptor substrate nationallicence IGF-I and IGF-II : insulin-like growth factor-I and-II nationallicence IGFBPs : insulin-like growth factor binding proteins nationallicence MBP : myelin basic protein nationallicence MT-1 : metallothionein-1 nationallicence P : postnatal day nationallicence PLP : proteolipid protein nationallicence Tg : transgenic nationallicence D'Ercole A. Department of Pediatrics CB# 7220, The University of North Carolina, 27599-7220, Chapel Hill, NC aut Ye Ping Department of Pediatrics CB# 7220, The University of North Carolina, 27599-7220, Chapel Hill, NC aut Calikoglu Ali Department of Pediatrics CB# 7220, The University of North Carolina, 27599-7220, Chapel Hill, NC aut Gutierrez-Ospina Gabriel Department of Pediatrics CB# 7220, The University of North Carolina, 27599-7220, Chapel Hill, NC aut Molecular Neurobiology Humana Press 13/3(1996-12-01), 227-255 0893-7648 13:3<227 1996 13 12035 https://doi.org/10.1007/BF02740625 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02740625 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- D'Ercole A. Department of Pediatrics CB# 7220, The University of North Carolina, 27599-7220, Chapel Hill, NC aut NATIONALLICENCE 700 1- Ye Ping Department of Pediatrics CB# 7220, The University of North Carolina, 27599-7220, Chapel Hill, NC aut NATIONALLICENCE 700 1- Calikoglu Ali Department of Pediatrics CB# 7220, The University of North Carolina, 27599-7220, Chapel Hill, NC aut NATIONALLICENCE 700 1- Gutierrez-Ospina Gabriel Department of Pediatrics CB# 7220, The University of North Carolina, 27599-7220, Chapel Hill, NC aut NATIONALLICENCE 773 0- Molecular Neurobiology Humana Press 13/3(1996-12-01), 227-255 0893-7648 13:3<227 1996 13 12035 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer