Expression of IGF‐I and insulin receptor genes in the rat central nervous system: A developmental, regional, and cellular analysis

Evercooren, A. Baron‐Van; Olichon-Berthe, C.; Kowalski, Aline; Visciano, G; Obberghen, Emmanuel Van

doi:10.1002/jnr.490280212

Cited by 118 publications

(44 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies using in situ hybridization and radiolabeled insulin suggest that insulin receptor mRNA and protein are widely expressed in brain (Havrankova et al, 1978;Baron Van Evercooren et al, 1991;Kar et al, 1997). However, insulin can bind to other cell surface proteins, including the insulin-like growth factor 1 receptor (IGF1R; Sosa et al, 2006), and therefore insulin binding may overestimate the extent of insulin receptor expression.…”

Section: Synapse Number Is Selectively Increased In Insulin Receptorementioning

confidence: 99%

“…However, insulin can bind to other cell surface proteins, including the insulin-like growth factor 1 receptor (IGF1R; Sosa et al, 2006), and therefore insulin binding may overestimate the extent of insulin receptor expression. To characterize insulin receptor protein expression in the brain, immunostaining was performed on permeabilized mouse brain sections using an antibody that is specific for insulin receptors and does not cross-react with IGF1Rs (EntinghPearsall and Kahn, 2004;Baudler et al, 2005). This antibody (clone C19) recognizes an intracellular epitope of the ␤-subunit of the insulin receptor.…”

Section: Synapse Number Is Selectively Increased In Insulin Receptorementioning

confidence: 99%

See 1 more Smart Citation

MHC Class I Limits Hippocampal Synapse Density by Inhibiting Neuronal Insulin Receptor Signaling

et al. 2014

View full text Add to dashboard Cite

Section: Synapse Number Is Selectively Increased In Insulin Receptorementioning

confidence: 99%

Section: Synapse Number Is Selectively Increased In Insulin Receptorementioning

confidence: 99%

MHC Class I Limits Hippocampal Synapse Density by Inhibiting Neuronal Insulin Receptor Signaling

et al. 2014

View full text Add to dashboard Cite

“…IGF-I gene expression is abundant in the developing nervous system (13)(14)(15)(16)(17)(18). IGF-I mRNA is selectively concentrated in the large principal neurons of functionally related sensory and cerebellar relay systems during a late predominantly postnatal phase of neural development (18).…”

mentioning

confidence: 99%

“…Also, several studies have shown that IGFs have potent and highly specific effects on oligodendrocytes in vitro (7)(8)(9)(10). However, except for the olfactory system, very little IGF-I is normally detected in the mature rodent brain (16)(17)(18).…”

mentioning

confidence: 99%

Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination.

Komoly

Hudson

Webster

et al. 1992

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

204

112

View full text Add to dashboard Cite

To investigate insulin-like growth factor I (IGF-I) and IGF-I receptor gene expression during experimental demyelination and myelin regeneration, young mice were fed cuprizone [bis (cyclohexanone) oxaldihydrazone]. This copper-chelating agent produces demyelination in the corpus callosum and superior cerebellar peduncles, and when treatment is stopped, there is rapid remyelination. At intervals during cuprizone treatment and recovery, brain sections were hybridized with specific probes and immunostained with antibodies to determine the localization and relative amounts of IGF-I and IGF-I receptor mRNAs and peptides. In untreated littermates, IGF-I and IGF-I receptor mRNAs and peptides were not detected in white matter. In cuprizone-treated mice, high levels of both IGF-I mRNA and peptide were expressed by astrocytes in areas of myelin breakdown. Astrocyte IGF-I expression decreased rapidly during recovery and oligodendroglial expression of myelin-related genes increased. In se- Insulin-like growth factor I (IGF-I), a member of the insulin gene family (1,2), has been shown to have a number ofpotent effects on cultured neural and glial cells. It promotes the mitosis of sympathetic neuroblasts, the survival of fetal neurons, and the stimulation of neurite outgrowth in motor and sensory neurons, and it induces oligodendrocyte differentiation and myelin synthesis (3-10). These effects are mediated by the type I IGF receptor, which is a membranebound tyrosine kinase with significant homology to the insulin receptor (11, 12). IGF-I gene expression is abundant in the developing nervous system (13-18). IGF-I mRNA is selectively concentrated in the large principal neurons of functionally related sensory and cerebellar relay systems during a late predominantly postnatal phase of neural development (18). The specific timing and cellular sites of neural IGF-I synthesis suggest a role for IGF-I in the synaptic maturation or the myelination of these particular systems. Evidence that IGF-I has a role in myelination is the finding that transgenic mice overexpressing IGF-I (19) have increased brain myelin content (20). Also, several studies have shown that IGFs have potent and highly specific effects on oligodendrocytes in vitro (7-10). However, except for the olfactory system, very little IGF-I is normally detected in the mature rodent brain (16-18).To investigate whether IGF-I is important in the regeneration of central nervous system myelin in vivo, demyelinating lesions were produced in the corpus callosum, superior cerebellar peduncles, and anterior commissures by adding the copper-chelating agent bis(cyclohexanone) oxaldihydrazone (cuprizone) to the diet of mice (21-23). In this model of primary demyelination, there are early severe changes in oligodendroglia and myelin sheaths in specific brain areas (21-23). Axons are relatively well preserved (21-23) and the blood-brain barrier remains impermeable to plasma proteins (24). There are no perivascular lymphocytic infiltrates (21,22) and the cessation of cuprizone tr...

show abstract

“…Moreover, astroglial cells appear to express an IGF1R similar to that found in peripheral cells (Baron-Van Evercooren et al 1991). Interestingly, these receptors differ from the IGF1Rs found in neurons, which have distinct glycosylated residues, as evidenced by in vitro studies (Burgess et al 1987).…”

Section: Discussionmentioning

confidence: 90%

Local overexpression of GH and GH/IGF1 effects in the adult mouse hippocampus

Walser¹,

Samà²,

Wickelgren³

et al. 2012

Journal of Endocrinology

View full text Add to dashboard Cite

GH therapy improves hippocampal functions mainly via circulating IGF1. However, the roles of local GH and IGF1 expression are not well understood. We investigated whether transgenic (TG) overexpression in the adult brain of bovine GH (bGH) under the control of the glial fibrillary acidic protein (GFAP) promoter affected cellular proliferation and the expression of transcripts known to be induced by systemic GH in the hippocampus. Cellular proliferation was examined by 5-bromo-2 0 -deoxyuridine immunohistochemistry. Quantitative PCR and western blots were performed. Although robustly expressed, bGH-Tg did not increase either cell proliferation or survival. However, bGH-Tg modestly increased Igf1 and Gfap mRNAs, whereas other GH-associated transcripts were unaffected, i.e. the GH receptor (Ghr), IGF1 receptor (Igf1r), 2 0 ,3 0 -cyclic nucleotide 3 0 -phosphodiesterase (Cnp), ionotropic glutamate receptor 2a (Nr2a (Grin2a)), opioid receptor delta (Dor), synapse-associated protein 90/postsynaptic density-95-associated protein (Sapap2 (Dlgap2)), haemoglobin beta (Hbb) and glutamine synthetase (Gs (Glul )). However, IGF1R was correlated with the expression of Dor, Nr2a, Sapap2, Gs and Gfap. In summary, although local bGH expression was robust, it activated local IGF1 very modestly, which is probably the reason for the low response of previous GH-associated response parameters. This would, in turn, indicate that hippocampal GH is less important than endocrine GH. However, as most transcripts were correlated with the expression of IGF1R, there is still a possibility for endogenous circulating or local GH to act via IGF1R signalling. Possible reasons for the relative bio-inactivity of bGH include the bell-shaped dose-response curve and cell-specific expression of bGH.

show abstract

Expression of IGF‐I and insulin receptor genes in the rat central nervous system: A developmental, regional, and cellular analysis

Cited by 118 publications

References 56 publications

MHC Class I Limits Hippocampal Synapse Density by Inhibiting Neuronal Insulin Receptor Signaling

MHC Class I Limits Hippocampal Synapse Density by Inhibiting Neuronal Insulin Receptor Signaling

Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination.

Local overexpression of GH and GH/IGF1 effects in the adult mouse hippocampus

Contact Info

Product

Resources

About