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

Calissano, Pietro; Ciotti, Maria Teresa; Battistini, Luca; Zona, Cristina; Angelini, Antonella; Merlo, Daniela; Mercanti, Delio

doi:10.1073/pnas.90.18.8752

Cited by 42 publications

(24 citation statements)

References 24 publications

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“…It has been recently reported that the coadministration of IGF-I and glutamate into the cerebellar cortex and the deep cerebellar nuclei greatly depresses the release of GABA, which normally follows a glutamate pulse and that electrical stimulation of the inferior olivary complex significantly raises IGF-I levels in the cerebellar cortex (Castro-Alamancos and Torres-Aleman, 1993). More recent findings suggest that the responsiveness of cerebellar granule cells to glutamate in vivo might be epigenetically regulated by IGF-I (Calissano et al, 1993). Taken together these data indicate a role for IGF-I in modulating the neural activity within certain areas of the mature CNS.…”

Section: Irs-i-immunoreactivesupporting

confidence: 48%

Insulin receptor substrate-1 (IRS-1) distribution in the rat central nervous system

et al. 1994

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Insulin receptor substrate 1 (IRS-1) is the primary cytosolic substrate of the insulin and insulin-like growth factor-I (IGF-I) receptors. Following tyrosine phosphorylation IRS-1 binds to and activates specific proteins containing SH2 domains. Using biochemical and immunocytochemical techniques, we have mapped the distribution of IRS-1 in the CNS of the adult rat and compared it with that of insulin and IGF-I receptors and phosphatidylinositol 3-kinase (PI-3 kinase), a signaling molecule functionally related to IRS-1. Immunoprecipitation and Western blotting experiments demonstrate the presence of substantial amounts of IRS-1, insulin receptor, and PI-3 kinase in the brain. IRS-1 immunoreactivity is widely distributed in neurons from several areas of the brain and spinal cord. The cerebral cortex, the hippocampus, many hypothalamic and thalamic nuclei, the basal ganglia, the cerebellar cortex, the brainstem nuclei, and the lamina X of the spinal cord are particularly rich of immunopositive nerve cells. In these areas most of the neurons immunoreactive for IRS-1 are also stained by either anti-insulin receptor or anti-IGF-I receptor antibodies as well as PI-3 kinase antiserum. IRS-1 immunostaining was very weak or totally absent in neurons of the olfactory bulb, the supraoptic and paraventricular nuclei, the mesencephalic trigeminal nucleus, and the granule cell layer of the cerebellum, despite the fact that these areas were immunolabeled with antibodies against insulin or IGF-I receptors and/or PI-3 kinase. These results show that neurons in the adult rat CNS are endowed with some of the components of the early signaling pathway for growth factors of the insulin/IGF-I family, although IRS-1 has a distribution distinct from that of the two receptors.

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Section: Irs-i-immunoreactivesupporting

confidence: 48%

Insulin receptor substrate-1 (IRS-1) distribution in the rat central nervous system

et al. 1994

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“…This neuroprotective effect of IGF-I was predominantly mediated by activation of PI3-K and Akt. However, IGF-I has also been reported to increase the sensitivity of cerebellar granule cells to NMDAinduced excitotoxicity (49). In contrast to granule cells, we demonstrate here that preincubation with IGF-I provides modest neuroprotection from NMDA-induced neuronal apoptosis in cerebrocortical cultures.…”

Section: Discussionmentioning

confidence: 42%

Acute neuroprotective synergy of erythropoietin and insulin-like growth factor I

Digicaylioglu

Garden

Timberlake

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

123

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Erythropoietin (EPO) and insulin-like growth factor I (IGF-I) are cytokines that inhibit neuronal apoptosis. However, their maximal antiapoptotic effect, even at high concentrations, is observed only when neurons are pretreated for several hours before insult. Here we show that simultaneous administration of EPO and IGF-I (EPO؉IGF-I) eliminates the preincubation period required to prevent N-methyl-D-aspartate (NMDA)-induced apoptosis in cultured rat cerebrocortical neurons. The synergistic effect of EPO؉IGF-I was mediated, at least in part, by activation of phosphatidylinositol 3-kinase (PI3-K). EPO؉IGF-I synergistically activated Akt (protein kinase B), a downstream target of PI3-K, and prevented dephosphorylation of Akt. Overexpression of a dominant interfering form of Akt (dnAkt) abrogated EPO؉IGF-I-mediated neuroprotection. EPO؉IGF-I treatment did not prevent initial NMDAinduced caspase-3 activation, which was observed within 6 h of insult; however, EPO؉IGF-I-treated neurons survived at least 2 days after NMDA insult. These cytokines prevented neuronal apoptosis downstream of caspase activation by facilitating association between X-linked inhibitor of apoptosis protein, an inhibitor of caspase proteolytic activity, and activated caspase-3. These results imply that EPO؉IGF-I exert cooperative actions that afford acute neuroprotection via activation of the PI3-K-Akt pathway.apoptosis ͉ phosphatidylinositol 3-kinase ͉ Akt (protein kinase B) ͉ X-linked inhibitor of apoptosis protein ͉ caspase-3

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“…Several lines of evidence have contributed to this co~ cept. Thus, IGF-1 induces the expression of functionally acl ve glutamate receptors in these neurons, and neutralizatio i of serum IGF-1 by a specific antibody reduces neuronal sul rival by 30-40% [29]. Although cerebellar granule neurons do not produce IGF-1 at any stage of development, they do ex I ,ress the IGF-1 receptor both in vivo [30] and in vitro (data no shown).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of protein phosphatases induces IGF‐1‐blocked neurotrophin‐insensitive neuronal apoptosis

et al. 1996

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We have previously described the marine toxin okadaic acid (OKA) to be a potent neurotoxin for cultured rat cerebeHar neurons. Here we show that OKA-induced neurodegeneration involves the DNA fragmentation characteristic of apoptosis and is protein synthesis-dependent. DNA fragmentation and neurotoxicity correlated with inhibition of protein phosphatase (PP) 2A rather than PP1 activity. Neurotrophins NT-3 and BDNF failed to protect from OKA-induced apoptotic neurotoxicity that was, however, totally prevented by insulin-like growth factor-1. Neuronal death by OKA was significantly reduced by protein kinase C inhibitors and by the L-type calcium channel agonist Bay K8644, while it was potentiated by the reduction of free extracellular calcium concentrations.

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

Cited by 42 publications

References 24 publications

Insulin receptor substrate-1 (IRS-1) distribution in the rat central nervous system

Insulin receptor substrate-1 (IRS-1) distribution in the rat central nervous system

Acute neuroprotective synergy of erythropoietin and insulin-like growth factor I

Inhibition of protein phosphatases induces IGF‐1‐blocked neurotrophin‐insensitive neuronal apoptosis

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