The IGF-I Amino-Terminal Tripeptide Glycine-Proline-Glutamate (GPE) Is Neuroprotective to Striatum in the Quinolinic Acid Lesion Animal Model of Huntington's Disease

Alexi, Tajrena; Hughes, Paul E.; Roon‐Mom, Willeke M. C. van; Faull, Richard L.M.; Williams, Chris; Clark, R. G.; Gluckman, Peter D.

doi:10.1006/exnr.1999.7168

Cited by 46 publications

(30 citation statements)

References 67 publications

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“…Our data confirm the previous observations about the relative survival of the different subtypes of striatal interneurons after QA lesions (Figueredo‐Cardenas et al ., 1994, 1997, 1998). The vulnerability of CALR interneurons after QA excitotoxicity is also confirmed by our study (Alexi et al ., 1999; Hughes et al ., 1999). Our study of the distribution of pCREB confirm its localization in the nuclei of all striatal neurons.…”

Section: Discussionsupporting

confidence: 89%

“…In particular, parvalbuminergic interneurons degenerate (Vonsattel & DiFiglia, 1998), whereas cholinergic, somatostatinergic (SS), and calretinin (CALR) interneurons survive in HD (Ferrante et al ., 1985; Ferrante et al ., 1986; Ferrante et al ., 1987; Albin et al ., 1990a; Cicchetti & Parent, 1996). Such diverse vulnerability was also observed in the quinolinic acid (QA) rat model of HD (Figueredo‐Cardenas et al ., 1998), with the exception of CALR interneurons, which degenerate rather early after QA lesions (Alexi et al ., 1999; Hughes et al ., 1999).…”

Section: Introductionmentioning

confidence: 99%

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Striatal modulation of cAMP‐response‐element‐binding protein (CREB) after excitotoxic lesions: implications with neuronal vulnerability in Huntington's disease

Giampà

DeMarch

D′Angelo

et al. 2005

Eur J of Neuroscience

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Recent evidence has shown that the activity of cAMP responsive element-binding protein (CREB) and of CREB-binding protein (CBP) is decreased in Huntington's disease (HD) [Steffan et al. (2000)Proc. Natl Acad. Sci. USA, 97, 6763-6768; Gines et al. (2003)Hum. Mol. Genet., 12, 497-508; Rouaux et al. (2004) Biochem. Pharmacol., 68, 1157-1164; Sugars et al. (2004)J. Biol. Chem., 279, 4988-4999]. Such decrease is thought to reflect the impaired energy metabolism observed in a HD mouse model, where a decline in striatum cAMP levels has been observed [Gines et al. (2003)Hum. Mol. Genet., 12, 497-508]. Increased levels of CREB have also been demonstrated to exert neuroprotective functions [Lonze & Ginty (2002)Neuron, 35, 605-623; Lonze et al. (2002)Neuron, 34, 371-385]. Our study aimed to investigate the distribution of CREB in the neuronal subpopulations of the striatum in normal rats compared to the HD model of quinolinic acid lesion. Twenty-five Wistar rats were administered quinolinic acid 100 mm into the right striatum, and killed after 24 h, 48 h, 1 week, 2 weeks, and six weeks, respectively. The contralateral striata were used as controls. Dual-label immunofluorescence was employed using antibodies against phosphorylated CREB and each of the different neuronal subpopulations markers. Our results show that activated CREB levels decrease progressively in projection neurons and parvalbumin (PARV) and calretinin (CALR) interneurons, whereas such levels remain stable in cholinergic and somatostatin interneurons. Thus, we speculate that the ability of cholinergic interneurons to maintain their levels of CREB after excitotoxic lesions is one of the factors determining their protection in Huntington's disease.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Striatal modulation of cAMP‐response‐element‐binding protein (CREB) after excitotoxic lesions: implications with neuronal vulnerability in Huntington's disease

Giampà

DeMarch

D′Angelo

et al. 2005

Eur J of Neuroscience

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“…Thus, administration of GPE protects neurons from NMDA-induced toxicity rat cortical slices, while central administration of GPE reduces the extent of cortical infarction in several models of hypoxia-ischemia in rats [15,16,17,18,29]. GPE has also been proved to be effective in preventing some of the clinical outcomes present in several animal models of degenerative diseases and, more recently, to exert an anti-depressant activity in mice [19,20,21,22]. In this study, we have described a novel effect of GPE in neural cells, such as the stimulation of cell proliferation and, to some extent, cell migration.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, GPE has been shown to protect hippocampal neurons from NMDA-induced toxicity in vitro [11], and to reduce brain injury after hypoxia-ischemia [16,17,18]. In addition, GPE has been found to exert neuroprotective actions in animal models of neurodegenerative processes, such as Huntington’s, Parkinson’s, or Alzheimer’s diseases [19,20,21]. Finally, GPE shows an anti-depressant activity in lipopolysaccharide (LPS)-induced depression in mice [22].…”

Section: Introductionmentioning

confidence: 99%

GPE Promotes the Proliferation and Migration of Mouse Embryonic Neural Stem Cells and Their Progeny In Vitro

Almengló

Devesa²,

Devesa³

et al. 2017

IJMS

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This study was designed to investigate a possible role of the N-terminal tripeptide of insulin-like growth factor-1 (IGF-I), Gly-Pro-Glu (GPE), physiologically generated in neurons following IGF-I-specific cleavage, in promoting neural regeneration after an injury. Primary cultures of mouse neural stem cells (NSCs), obtained from 13.5 Days post-conception (dpc) mouse embryos, were challenged with either GPE, growth hormone (GH), or GPE + GH and the effects on cell proliferation, migration, and survival were evaluated both under basal conditions and in response to a wound healing assay. The cellular pathways activated by GPE were also investigated by using specific chemical inhibitors. The results of the study indicate that GPE treatment promotes the proliferation and the migration of neural stem cells in vitro through a mechanism that involves the activation of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase PI3K-Akt pathways. Intriguingly, both GPE effects and the signaling pathways activated were similar to those observed after GH treatment. Based upon the results obtained from this study, GPE, as well as GH, may be useful in promoting neural protection and/or regeneration after an injury.

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“…One common link between IGF-I and GPE that may be related to their anti-depressant activity is their common ability to attenuate the activity of quinolinic acid [53,54]. Induction of tryptophan dioxygenase activity by inflammation plays a major role in depression as shunting of tryptophan metabolism toward the generation of metabolites such as quinolinic acid has been linked to inflammation-associated depression [55].…”

Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor-I peptides act centrally to decrease depression-like behavior of mice treated intraperitoneally with lipopolysaccharide

Park

Lawson

Dantzer

et al. 2011

J Neuroinflammation

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Centrally administered insulin-like growth factor (IGF)-I has anti-depressant activity in several rodent models, including lipopolysaccharide (LPS)-induced depression. In this study we tested the ability of IGF-I and GPE (the N-terminal tri-peptide derived from IGF-I) to alter depression-like behavior induced by intraperitoneal (i.p.) administration of LPS in a preventive and curative manner. In the first case, IGF-I (1 μg) or GPE (5 μg) was administered i.c.v. to CD-1 mice followed 30 min later by 330 μg/kg body weight i.p. LPS. In the second case, 830 μg/kg body weight LPS was given 24 h prior to either IGF-I or GPE. When administered i.p., LPS induced full-blown sickness assessed as a loss of body weight, decrease in food intake and sickness behavior. None of these indices were affected by IGF-I or GPE. LPS also induced depression-like behavior; assessed as an increased duration of immobility in the tail suspension and forced swim tests. When administered before or after LPS, IGF-I and GPE abrogated the LPS response; attenuating induction of depression-like behaviors and blocking preexistent depression-like behaviors. Similar to previous work with IGF-I, GPE decreased brain expression of cytokines in response to LPS although unlike IGF-I, GPE did not induce the expression of brain-derived neurotrophic factor (BDNF). LPS induced expression of tryptophan dioxygenases, IDO1, IDO2 and TDO2, but expression of these enzymes was not altered by GPE. Thus, both IGF-I and GPE elicit specific improvement in depression-like behavior independent of sickness, an action that could be due to their anti-inflammatory properties.

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The IGF-I Amino-Terminal Tripeptide Glycine-Proline-Glutamate (GPE) Is Neuroprotective to Striatum in the Quinolinic Acid Lesion Animal Model of Huntington's Disease

Cited by 46 publications

References 67 publications

Striatal modulation of cAMP‐response‐element‐binding protein (CREB) after excitotoxic lesions: implications with neuronal vulnerability in Huntington's disease

Striatal modulation of cAMP‐response‐element‐binding protein (CREB) after excitotoxic lesions: implications with neuronal vulnerability in Huntington's disease

GPE Promotes the Proliferation and Migration of Mouse Embryonic Neural Stem Cells and Their Progeny In Vitro

Insulin-like growth factor-I peptides act centrally to decrease depression-like behavior of mice treated intraperitoneally with lipopolysaccharide

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