Insulin-like growth factor I/somatomedin C: a potent inducer of oligodendrocyte development.

Abstract

Cell cultures established from cerebrum of 1-day-old rats were used to investigate hormonal regulation of the development of oligodendrocytes, which synthesize myelin in the central nervous system. The number of oligodendrocytes that developed was preferentially increased by insulin, or by insulin-like growth factor I (IGF-I), also known as somatomedin C. High concentrations (5 Pg/ml) of insulin were required for substantial induction of oligodendrocyte development, whereas only 3.3 ng of IGF-I per ml was needed for a 2-fold increase in oligodendrocyte numbers. At an IGF-I concentration of 100 ng/ml, oligodendrocyte numbers were increased 6-fold in cultures grown in the presence of 10% fetal bovine serum, or up to 60-fold in cultures maintained in serum-free medium. IGF-I produced less than a 2-fold increase in the number of nonoligodendroglial cells in the same cultures. Type I IGF receptors were identified on oligodendrocytes and on a putative oligodendrocyte precursor cell population identified by using mouse monoclonal antibody A2B5. These results indicate that IGF-I is a potent inducer of oligodendrocyte development and suggest a possible mechanism based on IGF deficiency for the hypomyelination that results from early postnatal malnutrition.Oligodendrocytes play a critical role in nervous system function by synthesizing and maintaining myelin in the central nervous system (CNS) (1). Very little is known about the stimuli or regulatory signals that promote the development of oligodendrocytes, but such information might provide the basis for approaches to promote repair in demyelinating disorders.We studied tissue cultures established from cerebrum of MATERIALS AND METHODS Cell Explantation and Culture. Cells were explanted by mechanical dissociation of cerebrum of 1-day-old strain LEC rats as described (3, 4) and were inoculated into polystyrene tissue culture dishes, glass microscope slide chambers, or dishes containing glass coverslips. Glass surfaces were previously treated with D-polylysine (10-50 pug/ml) or polylysine followed by fibronectin (1 Atg/cm2; purified by method B of ref. 9). Cells were maintained as mixed cultures without separation of individual cell types. Unless otherwise noted, culture medium was Eagle's minimum essential medium supplemented with glucose to a total of 6 g/liter, 0.1 mM of each nonessential amino acid, antibiotics, and 10% fetal bovine serum. For serum-free culture, cells were maintained in the presence of 10%6 fetal bovine serum for the first 16-24 hr of culture to allow the cells to attach (10, 11), and the cells were then rinsed and refed with serum-free culture medium. Serum-free medium (modified from ref. 10) consisted ofequal parts of Dulbecco's modified Eagle's medium (high-glucose formula) and Ham's F-12 medium, supplemented with glucose to a total of 6 g/liter/15 nM triiodothyronine/30 nM sodium selenite/transferrin (50 pug/ml). Insulin was absent except where noted. In all cases, medium was changed on the fourth day after explantation and every second da...

Role of Central Insulin-Like Growth Factor-1 Receptor Signalling in Ageing and Endocrine Regulation

“…The reduction of white matter was due to a net loss of axons and an additional shift from myelinated to unmyelintated fibres indicating the role of IGF-1 in axonal growth and/or maturation and its effect on the amount of oligodendrocytes and axon-myelination (Beck et al 1995). These findings are in line with many in vitro studies, which demonstrated a stimulating effect of IGF-1 on oligodendrocyte survival, development and proliferation (McMorris et al 1986;McMorris and Dubois-Dalcq 1988;Mozell and McMorris 1991). In addition, formation of hippocampal granule cells and striatal parvalbumin-containing neurons was reduced in IGF-1 -/-mice and therefore seems to require IGF-1 (Beck et al 1995).…”

“…IGFs regulate various cellular processes e.g. survival, differentiation and proliferation (McMorris et al 1986;McMorris & Dubois-Dalcq 1988;Mozell & McMorris 1991). Growth hormone, which induces IGF-1 secretion from the liver, is generated in the anterior pituitary and regulated by the hypothalamus via growth hormone releasing hormone (GHRH) and growth hormone inhibiting hormone (GHIH) Carlsson & Jansson 1990).…”

Insulin-like growth factor I in cultured rat astrocytes: expression of the gene, and receptor tyrosine kinase.

“…In our study IGF I was 5 S times more potent than IGF H. These results are in agreement with previous work by Lenoir and Honegger (1983), who observed that IGF I was significantly more potent than IGF II and insulin for stimulating thymidine incorporation 2-fold in fetal rat brain cells cultured in a chemically defined medium. Recently, McMorris et al (1986) In these studies IGF I was also much more potent that insulin.…”

Olfactory ensheathing cells: Historical perspective and therapeutic potential

“…Gal-C and MBP are two molecules that are expressed by myelinating glia as they assemble a myelin sheath. Oligodendrocytes, on the other hand, are known to synthesize significant levels of myelin-associated molecules in vitro, even in the absence of axonal contact, provided the growth medium contains insulin, hydrocortisone, or triiodothyronine (McMorris et al, 1986(McMorris et al, , 1990Lopes-Cardozo et al, 1989;Ved et al, 1989;Poduslo et al, 1990;Mozell and McMorris, 1991). These results point toward a different regulatory control over the promoter region of the MBP gene in oligodendrocytes and OECs Devon, 1994, 1995) in much the same way as this promoter region is believed to be controlled differently in oligodendrocytes and Schwann cells (Foran and Peterson, 1992;Gow et al, 1992).…”