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Redox Biol. 2017 Oct;13:69-81. doi: 10.1016/j.redox.2017.05.012. Epub 2017 May 26.

IGF-II promotes neuroprotection and neuroplasticity recovery in a long-lasting model of oxidative damage induced by glucocorticoids.

Author information

1
Department of Pharmacology and Paediatrics, Málaga University, Biomedical Research Institute of Málaga (IBIMA), Málaga, Spain.
2
Department of Human Physiology, Málaga University, Biomedical Research Institute of Málaga (IBIMA), Málaga, Spain.
3
Department of Life Sciences, University of Modena e Reggio Emilia, Modena, Italy.
4
Department of Psychobiology, Málaga University, Biomedical Research Institute of Málaga (IBIMA), Málaga, Spain.
5
Department of Pharmacology and Paediatrics, Málaga University, Biomedical Research Institute of Málaga (IBIMA), Málaga, Spain. Electronic address: pavia@uma.es.
6
Department of Human Physiology, Málaga University, Biomedical Research Institute of Málaga (IBIMA), Málaga, Spain. Electronic address: igf@uma.es.

Abstract

Insulin-like growth factor-II (IGF-II) is a naturally occurring hormone that exerts neurotrophic and neuroprotective properties in a wide range of neurodegenerative diseases and ageing. Accumulating evidence suggests that the effects of IGF-II in the brain may be explained by its binding to the specific transmembrane receptor, IGFII/M6P receptor (IGF-IIR). However, relatively little is known regarding the role of IGF-II through IGF-IIR in neuroprotection. Here, using adult cortical neuronal cultures, we investigated whether IGF-II exhibits long-term antioxidant effects and neuroprotection at the synaptic level after oxidative damage induced by high and transient levels of corticosterone (CORT). Furthermore, the involvement of the IGF-IIR was also studied to elucidate its role in the neuroprotective actions of IGF-II. We found that neurons treated with IGF-II after CORT incubation showed reduced oxidative stress damage and recovered antioxidant status (normalized total antioxidant status, lipid hydroperoxides and NAD(P) H:quinone oxidoreductase activity). Similar results were obtained when mitochondria function was analysed (cytochrome c oxidase activity, mitochondrial membrane potential and subcellular mitochondrial distribution). Furthermore, neuronal impairment and degeneration were also assessed (synaptophysin and PSD-95 expression, presynaptic function and FluoroJade B® stain). IGF-II was also able to recover the long-lasting neuronal cell damage. Finally, the effects of IGF-II were not blocked by an IGF-IR antagonist, suggesting the involvement of IGF-IIR. Altogether these results suggest that, in or model, IGF-II through IGF-IIR is able to revert the oxidative damage induced by CORT. In accordance with the neuroprotective role of the IGF-II/IGF-IIR reported in our study, pharmacotherapy approaches targeting this pathway may be useful for the treatment of diseases associated with cognitive deficits (i.e., neurodegenerative disorders, depression, etc.).

KEYWORDS:

Insulin-like growth factor-II; Insulin-like growth factor-II receptor; Mitochondria; Neuroprotection; Oxidative stress; Synapsis

PMID:
28575743
PMCID:
PMC5454142
DOI:
10.1016/j.redox.2017.05.012
[Indexed for MEDLINE]
Free PMC Article

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