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IGF-1 exacerbates the neurotoxicity of the mitochondrial inhibitor 3NP in rats.
Neurosci Lett. 2007 Oct 02; 425(3):167-72.NL

Abstract

Insulin-like Growth Factor 1 (IGF-1) has broad-range neuroprotective effects and is a therapeutic candidate for Huntington's disease (HD). IGF-1 protects striatal neurons from the toxicity of mutated huntingtin in vitro and improves neuronal survival in vivo in a phenotypic model of HD involving excitotoxic cell death. Because HD is a multifactorial disease, it is important to evaluate the neuroprotective role of IGF-1 in other pathological situations involved in HD progression. We have evaluated the neuroprotective effects of IGF-1 in vivo, using the 3-nitropropionic acid (3NP) rat model which replicates the mitochondrial dysfunction observed in HD. Continuous intracerebroventricular infusion of recombinant IGF-1 at a low dose (0.025 microg/h for 5 days) did not alleviate motor impairment and weight loss induced by 3NP treatment. In addition, histological evaluation and quantification of DNA fragmentation evidenced no improvement in neuronal survival. Of interest, we found that a higher concentration of IGF-1 (0.25 microg/h) resulted in an exacerbation of 3NP toxicity on striatal neurons. These results suggest that intracerebral delivery of IGF-1 may not provide a fully effective therapeutic strategy for HD or other disorders involving mitochondrial impairment.

Authors+Show Affiliations

CEA-DSV, I2BM, Service Hospitalier Frédéric Joliot, CNRS URA 2210, 4 place du Général Leclerc, 91401 Orsay, France. carolescartin@yahoo.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17868993

Citation

Escartin, Carole, et al. "IGF-1 Exacerbates the Neurotoxicity of the Mitochondrial Inhibitor 3NP in Rats." Neuroscience Letters, vol. 425, no. 3, 2007, pp. 167-72.
Escartin C, Boyer F, Bemelmans AP, et al. IGF-1 exacerbates the neurotoxicity of the mitochondrial inhibitor 3NP in rats. Neurosci Lett. 2007;425(3):167-72.
Escartin, C., Boyer, F., Bemelmans, A. P., Hantraye, P., & Brouillet, E. (2007). IGF-1 exacerbates the neurotoxicity of the mitochondrial inhibitor 3NP in rats. Neuroscience Letters, 425(3), 167-72.
Escartin C, et al. IGF-1 Exacerbates the Neurotoxicity of the Mitochondrial Inhibitor 3NP in Rats. Neurosci Lett. 2007 Oct 2;425(3):167-72. PubMed PMID: 17868993.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IGF-1 exacerbates the neurotoxicity of the mitochondrial inhibitor 3NP in rats. AU - Escartin,Carole, AU - Boyer,Frédéric, AU - Bemelmans,Alexis-Pierre, AU - Hantraye,Philippe, AU - Brouillet,Emmanuel, Y1 - 2007/08/19/ PY - 2007/06/14/received PY - 2007/08/04/revised PY - 2007/08/10/accepted PY - 2007/9/18/pubmed PY - 2007/12/15/medline PY - 2007/9/18/entrez SP - 167 EP - 72 JF - Neuroscience letters JO - Neurosci Lett VL - 425 IS - 3 N2 - Insulin-like Growth Factor 1 (IGF-1) has broad-range neuroprotective effects and is a therapeutic candidate for Huntington's disease (HD). IGF-1 protects striatal neurons from the toxicity of mutated huntingtin in vitro and improves neuronal survival in vivo in a phenotypic model of HD involving excitotoxic cell death. Because HD is a multifactorial disease, it is important to evaluate the neuroprotective role of IGF-1 in other pathological situations involved in HD progression. We have evaluated the neuroprotective effects of IGF-1 in vivo, using the 3-nitropropionic acid (3NP) rat model which replicates the mitochondrial dysfunction observed in HD. Continuous intracerebroventricular infusion of recombinant IGF-1 at a low dose (0.025 microg/h for 5 days) did not alleviate motor impairment and weight loss induced by 3NP treatment. In addition, histological evaluation and quantification of DNA fragmentation evidenced no improvement in neuronal survival. Of interest, we found that a higher concentration of IGF-1 (0.25 microg/h) resulted in an exacerbation of 3NP toxicity on striatal neurons. These results suggest that intracerebral delivery of IGF-1 may not provide a fully effective therapeutic strategy for HD or other disorders involving mitochondrial impairment. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/17868993/IGF_1_exacerbates_the_neurotoxicity_of_the_mitochondrial_inhibitor_3NP_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(07)00883-X DB - PRIME DP - Unbound Medicine ER -