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Increased Expression of Calcium/Calmodulin-Dependent Protein Kinase Type II Subunit Delta after Rat Traumatic Brain Injury

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Abstract

Many cellular responses to Ca2+ signals are mediated by Ca2+/calmodulin-dependent enzymes, among which is the Ca2+/calmodulin-dependent protein kinase II (CaMKII). CaMKII was originally described in rat brain tissue. In rat brain, four different subunits of the kinase have been identified: α, β, γ, and δ. This study aims to investigate changes of CaMKIIδ after traumatic brain injury and its possible role. Rat traumatic brain injury (TBI) model was established by controlled cortical injury system. In the present study, we mainly investigated the expression and cellular localization of CaMKIIδ after traumatic brain injury. Western blot analysis revealed that CaMKIIδ was present in normal rat brain cortex. It gradually increased, reached a peak at the third day after TBI, and then decreased. Importantly, more CaMKIIδ was colocalized with neuron. In addition, Western blot detection showed that the third day postinjury was also the apoptosis peak indicated by the elevated expression of caspase-3.Importantly, immunohistochemistry analysis revealed that injury-induced expression of CaMKIIδ was colabeled by caspase-3 (apoptosis cells marker). Moreover, pretreatment with the CaMKII inhibitor (KN62) reduced the injury-induced activation of caspase-3. Noticeably, the CaMKII inhibitor KN-62 could reduce TBI-induced cell injury assessed with lesion volume and attenuate behavioral outcome evaluated by motor test. These data suggested that CaMKIIδ may be implicated in the apoptosis of neuron and the recovery of neurological outcomes. However, the inherent mechanisms remained unknown. Further studies are needed to confirm the exact role of CaMKIIδ after brain injury.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No.30872666, No.81172911); Natural Science Foundation of Medical College of Nantong University (No.Y200905, No.Y201003); A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Authors and Affiliations

  1. Institute of Forensic Sciences, Soochow University, Suzhou, 215123, Jiangsu, China

    Mingyang Zhang, Tao Wang & Luyang Tao

  2. Department of Forensic Sciences, Medical College of Nantong University, Nantong, 226001, Jiangsu, China

    Mingyang Zhang, Zhenyong Gu & Donglin Wang

  3. Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

    Haiyan Shan & Zhiwei Wang

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  1. Mingyang Zhang
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  2. Haiyan Shan
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  3. Zhenyong Gu
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  4. Donglin Wang
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  5. Tao Wang
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  6. Zhiwei Wang
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Correspondence to Zhiwei Wang or Luyang Tao.

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M. Zhang and H. Shan contributed equally to this work.

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Zhang, M., Shan, H., Gu, Z. et al. Increased Expression of Calcium/Calmodulin-Dependent Protein Kinase Type II Subunit Delta after Rat Traumatic Brain Injury. J Mol Neurosci 46, 631–643 (2012). https://doi.org/10.1007/s12031-011-9651-y

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