Insulin‐like growth factor I stimulates oligodendrocyte development and myelination in rat brain aggregate cultures

Abstract

Insulin-like growth factor I (IGF-I) and high concentrations of insulin have been shown to stimulate an increase in the number of oligodendrocytes that appear in developing monolayer cultures of rat brain cells (McMorris et al., Proc Natl Acad Sci USA 83: 822-826, 1986; McMorris et al., Ann NY Acad Sci 605:101-109, 1990; McMorris and Dubois-Dalcq, J Neurosci Res 21:199-209, 1988). In the present study, we investigated whether IGF-I or insulin treatment induces a corresponding increase in the synthesis and accumulation of myelin. Aggregate cultures, established from 16-day-old fetal rat brains, were treated with either 100 ng/ml IGF-I or 5,000 ng/ml insulin and analyzed for the number of oligodendrocytes, activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), total amount of myelin, and synthesis rate of myelin proteins. Cultures treated with IGF-I beginning on day 2 after explantation contained 35-80% more oligodendrocytes and had 60-160% higher CNP activity than controls when tested on day 13, 20, or 27. By day 27, treated cultures had 35-90% more myelin than controls. Similar results were observed in response to 5,000 ng/ml insulin, a concentration at which insulin binds to IGF receptors and acts as an analogue of IGF-I. The synthesis rate of myelin proteins was measured in experiments using 5,000 ng/ml insulin. When treatment was begun at day 20 rather than day 2, cultures did not exhibit an increased number of oligodendrocytes over control during the following 4-6 days.(ABSTRACT TRUNCATED AT 250 WORDS)

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 (IGF) Signaling through Type 1 IGF Receptor Plays an Important Role in Remyelination

“…Systemic administration of IGF-1 enhances remyelination by inhibiting the immune response in some autoimmune models of demyelination (Liu et al, 1997;Li et al, 1998), but not in others (Cannella et al, 2000). Although IGF-1 induces the differentiation of oligodendrocyte progenitors in vitro (McMorris and Dubois-Dalq, 1988;Mozell and McMorris, 1991;Barres et al, 1993) and is upregulated within remyelinating lesions in cuprizone-, experimental autoimmune encephalomyelitis-, and lysolecithininduced demyelination (Liu et al, 1994; Figure 6. Effects of IGF signaling on the accumulation of oligodendrocyte progenitors.…”

“…IGF-1 is a survival factor for oligodendrocytes (Barres et al, 1993;Ye and D'Ercole, 1999;Mason et al, 2000b) and a differentiation factor for neonatal (McMorris and Dubois-Dalq, 1988;Mozell and McMorris, 1991) and adult (Mason and Goldman, 2002) oligodendrocyte progenitors in vitro. Its levels are elevated within demyelinating and remyelinating lesions in the adult CNS (Liu et al, 1994;Yao et al, 1995;Mason et al, 2000a).…”

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).…”