Oncotarget

Research Papers:

Postnatal calpain inhibition elicits cerebellar cell death and motor dysfunction

Junyao Li, Sanjuan Yang and Guoqi Zhu _

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Oncotarget. 2017; 8:87997-88007. https://doi.org/10.18632/oncotarget.21324

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Abstract

Junyao Li1, Sanjuan Yang1 and Guoqi Zhu1

1Key Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230038, China

Correspondence to:

Guoqi Zhu, email: [email protected]

Keywords: postnatal, calpain inhibition, cerebellum, apoptosis, motor dysfunction

Abbreviations: SBPs: spectrin breakdown products; RFU: relative fluorescence unit; p-Akt: phosphorylated protein kinase B; SCOP: suprachiasmatic nucleus circadian oscillatory protein.

Received: July 25, 2017     Accepted: August 29, 2017     Published: September 27, 2017

ABSTRACT

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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