Survival of Purkinje Cells in Cerebellar Cultures is Increased by Insulin‐like Growth Factor I

Abstract

Insulin‐like growth factor I (IGF‐I) is a trophic factor for both neurons and glia. Its presence in the developing and adult cerebellum suggests a role for this growth factor in this area of the brain. Recently, we have described the existence of an IGF‐I‐containing pathway in afferents of Purkinje neurons arising from the inferior olive. In addition, IGF‐I receptors are present in the molecular layer of the cerebellar cortex. These observations prompted us to investigate whether the Purkinje cell is a target for IGF‐I. Addition of IGF‐I to rat cerebellar cultures produced a 7‐fold increase in the number of Purkinje cells (calbindin‐positive) together with an increase in the calbindin content of the cultures. IGF‐I also doubled the number of surviving neurons and produced a moderate, non‐significant increase in [3H]thymidine incorporation by the cultures. On the other hand, basic fibroblast growth factor (bFGF), which is also present in the cerebellum, produced a dramatic increase in both the proportion of astrocytes and in the mitotic activity of the cultures, without affecting neuron survival. We conclude that IGF‐I is a specific promoter of Purkinje cell survival and that its effects differ from those produced by bFGF in fetal cerebellar cultures. These findings reinforce our hypothesis that the Purkinje cell is a target neuron for IGF‐I action in the developing cerebellum.

Recombinant human insulin-like growth factor I exerts a trophic action and confers glutamate sensitivity on glutamate-resistant cerebellar granule cells.

“…4 c and d) (Fig. 4d) (19)(20)(21), and the same neurons respond in vitro to IGF-I with improved survival (22 (Fig. 2) upregulation of glutamate-activated Ca2+ channels, we hypothesize that the two phenomena are causally related.…”

“…Dissociated cells suspended in basal medium with Eagle's salts (BME), 25 mM KCl, 2 mM glutamine, and gentamicin (100 jig/ml) were plated at 2.5 x 106 per dish in poly(Llysine)-coated dishes (Nunc). At plating, 10% heatinactivated FBS or NOAC (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) pg/ml) plus the factor to be tested was added to the medium. After 18-20 hr 10 pM 1-,fD-arabinofuranosylcytosine was added to prevent nonneuronal cell replication.…”

Low Insulin‐Like Growth Factor (IGF‐1) in the Cerebrospinal Fluid of Children with Progressive Encephalopathy, Hypsarrhythmia, and Optic Atrophy (PEHO) Syndrome and Cerebellar Degeneration

“…Levels of IGF-I vary both regionally and developmentally (37,38). IGF-1 has been shown to promote survival of cerebellar neurons (23,24), granular cells (39,40), and oligodendroglia (4 1) significantly by inhibiting apoptosis. IGF-1 is a potent mitogen for cerebellar granule cell neuroblasts in vitro (40).…”

“…Compelling evidence that IGF-1 has a key role in brain development was obtained recently from studies in transgenic and gene knockout mice (18). Animal models of neurodegeneration have shown evidence of local changes in the levels of IGF-I and its related molecules (19)(20)(21), and IGF-1 has been shown to significantly promote the survival of cerebellar neurons in vitro (22)(23)(24).…”

The decrease in hepatic IGF-I gene expression in arthritic rats is not associated with modifications in hepatic GH receptor mRNA

“…Liver IGF-I was extracted as described by TorresAleman et al (15). Samples were homogenized in 1 M acetic acid, boiled for 20 min, and lyophilized.…”