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Serotonin/5-HT1A Signaling in the Neurovascular Unit Regulates Endothelial CLDN5 Expression.
Sugimoto, Kotaro; Ichikawa-Tomikawa, Naoki; Nishiura, Keisuke; Kunii, Yasuto; Sano, Yasuteru; Shimizu, Fumitaka; Kakita, Akiyoshi; Kanda, Takashi; Imura, Tetsuya; Chiba, Hideki.
Afiliação
  • Sugimoto K; Department of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
  • Ichikawa-Tomikawa N; Department of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
  • Nishiura K; Department of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
  • Kunii Y; Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
  • Sano Y; Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan.
  • Shimizu F; Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan.
  • Kakita A; Department of Pathology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
  • Kanda T; Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan.
  • Imura T; Department of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
  • Chiba H; Department of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
Int J Mol Sci ; 22(1)2020 Dec 29.
Article em En | MEDLINE | ID: mdl-33383868
ABSTRACT
We previously reported that site-selective claudin-5 (CLDN5) breakdown and protein kinase A (PKA) activation are observed in brain microvessels of schizophrenia, but the underlying molecular basis remains unknown. The 5-HT1 receptors decline the intracellular cAMP levels and inactivate the major downstream PKA, and the 5-HT1A receptor is a promising target for schizophrenia. Therefore, we elucidated the involvement of serotonin/5-HT1A signaling in the endothelial CLDN5 expression. We demonstrate, by immunohistochemistry using post-mortem human brain tissue, that the 5-HT1A receptor is expressed in brain microvascular endothelial cells (BMVECs) and mural cells of the normal prefrontal cortex (PFC) gray matter. We also show that PKA is aberrantly activated not only in BMVECs but also in mural cells of the schizophrenic PFC. We subsequently revealed that the endothelial cell-pericyte tube-like structure was formed in a novel two-dimensional co-culture of human primary BMVECs and a human brain-derived pericyte cell line, in both of which the 5-HT1A receptor was expressed. Furthermore, we disclose that the serotonin/5-HT1A signaling enhances endothelial CLDN5 expression in BMVECs under two-dimensional co-culture conditions. Our findings provide novel insights into the physiological and pathological significance of serotonin/5-HT1A signaling in the region-specific regulation of the blood-brain barrier.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Serotonina / Regulação da Expressão Gênica / Células Endoteliais / Receptor 5-HT1A de Serotonina / Claudina-5 / Acoplamento Neurovascular Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Serotonina / Regulação da Expressão Gênica / Células Endoteliais / Receptor 5-HT1A de Serotonina / Claudina-5 / Acoplamento Neurovascular Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article