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Intracerebroventricular administration of an endothelin ET B receptor agonist increases expressions of GDNF and BDNF in rat brain
Author(s) -
Koyama Yutaka,
Tsujikawa Kimiko,
Matsuda Toshio,
Baba Akemichi
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02797.x
Subject(s) - glial cell line derived neurotrophic factor , endocrinology , medicine , neurotrophic factors , endothelins , agonist , astrocyte , receptor , brain derived neurotrophic factor , chemistry , biology , endothelin receptor , central nervous system
Endothelins (ETs) are suggested to be involved in functional alterations of astrocytes after brain injury, including proliferation, hypertrophy and production of neurotrophic factors. In this study, effects of Ala 1,3,11,15 ‐endothelin‐1 (Ala 1,3,11,15 ‐ET‐1), an ET B receptor selective agonist, on neurotrophic factor production were examined in rat brain. A continuous intracerebroventricular administration of Ala 1,3,11,15 ‐ET‐1 (500 pmol/day for 7 days) increased the numbers of GFAP‐ and vimentin‐positive astrocytes in the hippocampus, caudate putamen and cerebrum. Ala 1,3,11,15 ‐ET‐1 did not induce neuronal degeneration and activation of microglia/macrophage in these brain regions. The intracerebroventricular administration of Ala 1,3,11,15 ‐ET‐1 for 7 days caused two‐ to three‐fold increases in glial cell line‐derived neurotrophic factors (GDNF) mRNA in the hippocampus and cerebrum. The mRNA levels of brain‐derived neurotrophic factors (BDNF) in caudate putamen were increased by Ala 1,3,11,15 ‐ET‐1. Expressions of nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) mRNA in these regions were not largely affected by Ala 1,3,11,15 ‐ET‐1, except cerebral NGF mRNA level was increased. The Ala 1,3,11,15 ‐ET‐1‐induced increases in GDNF and BDNF mRNA levels were accompanied by increases in immunoreactive GDNF and BDNF. Immunohistochemical observations showed that GFAP‐positive astrocytes expressed GDNF and BDNF in the brain regions of Ala 1,3,11,15 ‐ET‐1‐infused rats. In cultured rat astrocytes, Ala 1,3,11,15 ‐ET‐1 (100 n m ) increased mRNA levels of GDNF and BDNF. These results suggest that activation of brain ET B receptors induced GDNF and BDNF expression in astrocytes.