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Pericyte-derived Glial Cell Line-derived Neurotrophic Factor Increase the Expression of Claudin-5 in the Blood–brain Barrier and the Blood-nerve Barrier

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Abstract

The destruction of blood–brain barrier (BBB) and blood-nerve barrier (BNB) has been considered to be a key step in the disease process of a number of neurological disorders including cerebral ischemia, Alzheimer’s disease, multiple sclerosis, and diabetic neuropathy. Although glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) facilitate neuronal or axonal regeneration in the brain or peripheral nerves, their action in the BBB and BNB remains unclear. The purpose of the present study was to elucidate whether these neurotrophic factors secreted from the brain or peripheral nerve pericytes increase the barrier function of the BBB or BNB, using our newly established human brain microvascular endothelial cell (BMEC) line or peripheral nerve microvascular endothelial cell (PnMEC) line. GDNF increased the expression of claudin-5 and the transendothelial electrical resistance (TEER) of BMECs and PnMECs, whereas BDNF did not have this effect. Furthermore, we herein demonstrate that the GDNF secreted from the brain and peripheral nerve pericytes was one of the key molecules responsible for the up-regulation of claudin-5 expression and the TEER value in the BBB and BNB. These results indicate that the regulation of GDNF secreted from pericytes may therefore be a novel therapeutic strategy to modify the BBB or BNB functions and promote brain or peripheral nerve regeneration.

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Acknowledgments

This work was supported by research grants (Nos. 22790821 and Nos. 21390268) from the Japan Society for the Promotion of Science, Tokyo, Japan and also by research grant (K2002528) from Health and Labor Sciences Research Grants for research on intractable diseases (Neuroimmunological Disease Research Committee) from the Ministry of Health, Labor and Welfare of Japan.

Conflict of interest

The authors declare that there is no duality of interest associated with this manuscript.

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Authors and Affiliations

  1. Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1, Minamikogushi, Ube, Yamaguchi, 7558505, Japan

    Fumitaka Shimizu, Yasuteru Sano, Masa-aki Abe, Toshihiko Maeda, Hiroyo Haruki & Takashi Kanda

  2. Department of Neurology and Clinical Neuroscience, Tokyo Medical and Dental Graduate School of Medicine, Tokyo, Japan

    Kazuyuki Saito

Authors
  1. Fumitaka Shimizu
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  2. Yasuteru Sano
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  3. Kazuyuki Saito
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  4. Masa-aki Abe
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  5. Toshihiko Maeda
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  6. Hiroyo Haruki
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  7. Takashi Kanda
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Correspondence to Takashi Kanda.

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Special issue: In honor of Dr. Abel Lajtha.

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Shimizu, F., Sano, Y., Saito, K. et al. Pericyte-derived Glial Cell Line-derived Neurotrophic Factor Increase the Expression of Claudin-5 in the Blood–brain Barrier and the Blood-nerve Barrier. Neurochem Res 37, 401–409 (2012). https://doi.org/10.1007/s11064-011-0626-8

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  • DOI: https://doi.org/10.1007/s11064-011-0626-8

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