Insulin‐like growth factor I promotes cell proliferation and oligodendroglial commitment in rat glial progenitor cells developing in vitro

Abstract

We investigated the mechanisms by which insulin-like growth factor I (IGF-I) acts to increase the number of oligodendrocytes that develop in cultures of cells explanted from perinatal rat cerebrum. Fluorescence-activated cell sorting was used to isolate bipotential A2B5-positive oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells, which were then inoculated as single cells into microculture wells containing feeder layers of X-irradiated type 1 astrocytes. Addition of 100 ng/ml IGF-I to the culture medium increased the growth rate and the ultimate size reached by the resulting clones during the 18-day experimental period. Moreover, 75-80% of the cells in the IGF-I-treated clones differentiated into galactocerebroside (GC)-positive oligodendrocytes, whereas only 25-30% became oligodendrocytes in the absence of IGF-I. IGF-I did not increase the number of type 2 astrocytes that developed in the clones. IGF-I appeared to have the greatest effect on growth and differentiation at a stage when the majority of the cells in the clones were at an intermediate stage of development, characterized by the expression of A2B5 and O4 glycolipid antigens but not GC. Analysis of the effects of IGF-I on O4-positive, GC-negative intermediate precursor cells revealed a two to fivefold increase in the number of cells that incorporated 3H-thymidine into their DNA during a 5-h pulse. Moreover, IGF-I increased the number of cell sorter-purified O4-positive cells that developed into oligodendrocytes 4-8 days later. Therefore, IGF-I acts in two different ways to promote oligodendrocyte development: It promotes proliferation of precursor cells in the O-2A lineage, and it induces precursors to become committed to develop into oligodendrocytes.

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).…”

Reversible inhibition of oligodendrocyte progenitor differentiation by a monoclonal antibody against surface galactolipids.

“…The differentiation of 04+GalC-progenitors into OLs is responsive to environmental cues, such as insulin-like growth factor I (17). Subsequently, additional myelin-specific markers appear in an ordered temporal sequence, including first GalC, sulfatide, and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), followed by proteolipid protein, and finally myelin basic protein (MBP) (3,9).…”

Oligodendrocyte Fate after Spinal Cord Injury

“…Another important factor in promoting OPC proliferation and OL survival is insulin-like growth factor (IGF) [91,92]. IGF may play a role in oligogenesis after SCI as increased astrocytic production of IGF-1 was noted in a cryogenic SCI model [93].…”