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Investigation of Mature BDNF and proBDNF Signaling in a Rat Photothrombotic Ischemic Model

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Abstract

Treatment with mature brain-derived neurotrophic factor (mBDNF) promotes functional recovery after ischemia in animal trials but the possible role of its precursor protein proBDNF and its receptors or the factors responsible for the conversion of proBDNF to mBDNF in ischemic stroke are not known. The main aim of this study was to characterize the time-dependent expression of genes and/or proteins related to BDNF processing and signaling after ischemia as well as the sensorimotor behavioral dysfunction in a photothrombotic ischemic model in rats. Characterization of different genes and proteins related to BDNF processing and signaling was performed using qPCR, immunoblotting and enzyme-linked immunosorbent assays. We showed in this study that some sensory and motor functional deficiencies appeared in the ischemic group at day 1 and persisted until day 14. Most changes in gene expression of BDNF and its processing enzymes occurred within the first 24 h in the ipsilateral cortex, but not in the contralateral cortex. At the protein level, proBDNF expression was increased at 6 h, mBDNF expression was increased between 15 h and 1 day while p75 receptor protein expression was increased between 6 h and 3 days in the ipsilateral cortex, but not in the contralateral cortex. Therefore, cerebral ischemia in rats led to the up-regulation of genes and/or proteins of BDNF, proBDNF and their processing enzymes and receptors in a time-dependent manner. We propose that the balance between BDNF and proBDNF and their associated proteins may play an important role in the pathogenesis and recovery from ischemia.

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Acknowledgements

This work was supported by the National Health and Medical Research Council (NHMRC) and Sansom Institute for Health Research (University of South Australia). Mehreen Rahman is a recipient of the International Postgraduate Research Scholarship (Australia). We are also thankful to the Reid Animal Facility staff members for their support throughout this study.

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Authors and Affiliations

  1. School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, 5000, Australia

    Mehreen Rahman, Haiyun Luo, Larisa Bobrovskaya & Xin-Fu Zhou

  2. Department of Pharmacology, Kunming Medical University, Kunming, China

    Haiyun Luo

  3. Discipline of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, SA, Australia

    Neil R. Sims

Authors
  1. Mehreen Rahman
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  2. Haiyun Luo
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  3. Neil R. Sims
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  4. Larisa Bobrovskaya
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  5. Xin-Fu Zhou
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Contributions

MR and HL performed the experiments; NS assisted with developing the photothrombotic model and manuscript preparation; XFZ and LB designed the experiments; MR, LB, and XFZ wrote the manuscript.

Corresponding authors

Correspondence to Larisa Bobrovskaya or Xin-Fu Zhou.

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Conflict of interest

There is no conflict of interests to declare by the authors. The original data is stored in the server of the University of South Australia and it is accessible if required.

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Rahman, M., Luo, H., Sims, N.R. et al. Investigation of Mature BDNF and proBDNF Signaling in a Rat Photothrombotic Ischemic Model. Neurochem Res 43, 637–649 (2018). https://doi.org/10.1007/s11064-017-2464-9

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  • DOI: https://doi.org/10.1007/s11064-017-2464-9

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