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Postnatal calpain inhibition elicits cerebellar cell death and motor dysfunction

Calpain-1 deletion elicits neurodevelopmental disorders, such as ataxia. However, the function of calpain in postnatal neurodevelopment and its mechanisms remain unknown. In this study, we revealed that postnatal intraperitoneal injection of various calpain inhibitors attenuated cerebellar cytosolic...

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Detalles Bibliográficos
Autores principales: Li, Junyao, Yang, Sanjuan, Zhu, Guoqi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675688/
https://www.ncbi.nlm.nih.gov/pubmed/29152136
http://dx.doi.org/10.18632/oncotarget.21324
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author Li, Junyao
Yang, Sanjuan
Zhu, Guoqi
author_facet Li, Junyao
Yang, Sanjuan
Zhu, Guoqi
author_sort Li, Junyao
collection PubMed
description Calpain-1 deletion elicits neurodevelopmental disorders, such as ataxia. However, the function of calpain in postnatal neurodevelopment and its mechanisms remain unknown. In this study, we revealed that postnatal intraperitoneal injection of various calpain inhibitors attenuated cerebellar cytosolic calpain activity. Moreover, postnatal application of calpeptin (2 mg/kg) apparently reduced spectrin breakdown, promoted suprachiasmatic nucleus circadian oscillatory protein (SCOP) accumulation in cerebellar tissue. In addition, application of calpeptin decreased phosphorylated protein kinase B (p-AKT) level (p<0.05), as well as total AKT level (p<0.05). We also evidenced that administration of calpeptin obviously increased phosphorylation of mammalian target of rapamycin (p-mTor) (p<0.01). Apoptosis of granular cells and activation of caspase-3 (p<0.01) were facilitated after calpain inhibition. Importantly, cell numbers of granular cells were reduced and motor function was remarkably impaired in 4-month-old rats receiving postnatal calpain inhibition. Taken together, our data implicated that calpain activity in the postnatal period was critical for the cerebellar development. Postnatal calpain inhibition causes cerebellar granular cell apoptosis and motor dysfunction, likely through SCOP/AKT and p-mTor signaling pathways.
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spelling pubmed-56756882017-11-18 Postnatal calpain inhibition elicits cerebellar cell death and motor dysfunction Li, Junyao Yang, Sanjuan Zhu, Guoqi Oncotarget Research Paper Calpain-1 deletion elicits neurodevelopmental disorders, such as ataxia. However, the function of calpain in postnatal neurodevelopment and its mechanisms remain unknown. In this study, we revealed that postnatal intraperitoneal injection of various calpain inhibitors attenuated cerebellar cytosolic calpain activity. Moreover, postnatal application of calpeptin (2 mg/kg) apparently reduced spectrin breakdown, promoted suprachiasmatic nucleus circadian oscillatory protein (SCOP) accumulation in cerebellar tissue. In addition, application of calpeptin decreased phosphorylated protein kinase B (p-AKT) level (p<0.05), as well as total AKT level (p<0.05). We also evidenced that administration of calpeptin obviously increased phosphorylation of mammalian target of rapamycin (p-mTor) (p<0.01). Apoptosis of granular cells and activation of caspase-3 (p<0.01) were facilitated after calpain inhibition. Importantly, cell numbers of granular cells were reduced and motor function was remarkably impaired in 4-month-old rats receiving postnatal calpain inhibition. Taken together, our data implicated that calpain activity in the postnatal period was critical for the cerebellar development. Postnatal calpain inhibition causes cerebellar granular cell apoptosis and motor dysfunction, likely through SCOP/AKT and p-mTor signaling pathways. Impact Journals LLC 2017-09-27 /pmc/articles/PMC5675688/ /pubmed/29152136 http://dx.doi.org/10.18632/oncotarget.21324 Text en Copyright: © 2017 Li et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Li, Junyao
Yang, Sanjuan
Zhu, Guoqi
Postnatal calpain inhibition elicits cerebellar cell death and motor dysfunction
title Postnatal calpain inhibition elicits cerebellar cell death and motor dysfunction
title_full Postnatal calpain inhibition elicits cerebellar cell death and motor dysfunction
title_fullStr Postnatal calpain inhibition elicits cerebellar cell death and motor dysfunction
title_full_unstemmed Postnatal calpain inhibition elicits cerebellar cell death and motor dysfunction
title_short Postnatal calpain inhibition elicits cerebellar cell death and motor dysfunction
title_sort postnatal calpain inhibition elicits cerebellar cell death and motor dysfunction
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675688/
https://www.ncbi.nlm.nih.gov/pubmed/29152136
http://dx.doi.org/10.18632/oncotarget.21324
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