Elsevier

Brain Research

Volume 994, Issue 2, 24 December 2003, Pages 253-259
Brain Research

Short communication
Immunohistochemical study on the distribution of insulin-like growth factor I (IGF-I) receptor in the central nervous system of SOD1G93A mutant transgenic mice

https://doi.org/10.1016/j.brainres.2003.09.047Get rights and content

Abstract

In the present study, we used the SOD1G93A mutant transgenic mice as an in vivo model of ALS and performed immunohistochemical studies to investigate the changes of insulin-like growth factor I (IGF-I) receptor in the central nervous system. IGF-I receptor-immunoreactive astrocytes were detected in the spinal cord, brainstem, central gray and cerebellar nuclei of SOD1G93A transgenic mice. In contrast to transgenic mice, no IGF-I receptor-immunoreactive astrocytes were observed in any brain region of wtSOD1 transgenic mice although a few moderately stained neurons were observed. In the hippocampal formation of SOD1G93A transgenic mice, IGF-I receptor immunoreactivity was increased in the pyramidal cells of the CA1-3 regions and granule cells of the dentate gyrus. The present study provides the first evidence that IGF-I receptor immunoreactivity was increased in reactive astrocytes in the central nervous system of SODG93A transgenic mice, suggesting that reactive astrocytes may play an important role in the pathogenesis and progress of ALS. The mechanisms underlying the increased immunoreactivity for IGF-I receptor, and the functional implications of these increases, require elucidation.

Section snippets

Acknowledgements

This study was supported by Seoul National University Hospital Research Fund (03-2003-002). This study was supported in part by year 2003 BK21 project for Medicine, Dentistry and Pharmacy.

References (28)

Cited by (24)

  • Molecular classification of amyotrophic lateral sclerosis by unsupervised clustering of gene expression in motor cortex

    2015, Neurobiology of Disease
    Citation Excerpt :

    Differential expression of Angiotensin II and its type-1 receptor may be linked to the altered levels of Angiotensin II found in liquor of ALS patients (Kawajiri et al., 2009), whereas that of Leukemia inhibitory factor (LIF) and its receptor are consistent with a study proposing LIF as a modifier gene in ALS (Giess et al., 2000). The up regulation of IGF1 receptor is in agreement with previous studies (Chung et al., 2003; Wilczak et al., 2003), whereas that of purinergic receptor P2Y2 supports the role for P2 receptor signaling in ALS (D'Ambrosi et al., 2009). A number of genes encoding proteins regulation ion homeostasis were deregulated in motor cortex of SALS patients (Fig. 9).

  • Insulin-Like Growth Factors in the Peripheral Nervous System

    2012, Endocrinology and Metabolism Clinics of North America
    Citation Excerpt :

    In the wobbler mouse, a model of lower MN degeneration, subcutaneous IGF-I treatment improves motor function.111 Examination of an ALS mouse model indicates that mutant SOD1 expression in Schwann cells induces diminished IGF-I levels in nerves that enhance disease progression,112 and that increased IGF-I expression is observed in astrocytes in the spinal cord.113 Subcutaneous administration of IGF-I in ALS mice, however, demonstrates no significant impact on survival.104

  • Motor neuron trophic factors: Therapeutic use in ALS?

    2011, Brain Research Reviews
    Citation Excerpt :

    IGF-1 receptors are expressed not only by MNs but also by oligodendrocytes, Schwann cells, astrocytes, smooth and skeletal muscle cells and endothelial cells, indicating a plethora of potential cellular non-autonomous mechanisms by which IGF-1 could regulate MN disease. Evidence for such signaling is provided by the finding that although the serum or spinal cord levels of IGF-1 are normal in ALS patients (Braunstein and Reviczky, 1987; Adem et al., 1994), increased astrocytic IGF-1 receptor expression is observed in the spinal cord of human ALS patients and fALS mice (Adem et al., 1994; Chung et al., 2003; Dagvajantsan et al., 2008). When administered at symptom onset, exogenous IGF-1 attenuates the loss of muscle weight and decline of behavioural performance in wobbler mutant mice (Hantaï et al., 1995).

  • Interactions of estradiol and insulin-like growth factor-I signalling in the nervous system: New advances

    2010, Progress in Brain Research
    Citation Excerpt :

    In addition to the neuroprotective effects of peripheral IGF-I, local IGF-I produced in the nervous system may also play a role in neuroprotection. Brain injury induces the synthesis of IGF-I and estradiol by reactive astrocytes (Garcia-Estrada et al., 1992; Garcia-Segura, 2008; Hwang et al., 2004; Saldanha et al., 2009) and up-regulates ERs, IGF-I receptors, and IGF-binding proteins in reactive glia (Beilharz et al., 1998; Blurton-Jones and Tuszynski, 2001; Chung et al., 2003; Garcia-Ovejero et al., 2002). Therefore, estradiol and IGF-I released by reactive glia may act directly on these cells or on neighbouring neurons, regulating reactive gliosis, neuronal survival and the reorganization of neural tissue after injury.

View all citing articles on Scopus
View full text