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Adenosine A 2B receptor down‐regulates metabotropic glutamate receptor 5 in astrocytes during postnatal development
Author(s) -
Tanaka Masayoshi,
Shigetomi Eiji,
Parajuli Bijay,
Nagatomo Hiroaki,
Shinozaki Youichi,
Hirayama Yuri,
Saito Kozo,
Kubota Yuto,
Danjo Yosuke,
Lee Ji Hwan,
Kim Sun Kwang,
Nabekura Junichi,
Koizumi Schuichi
Publication year - 2021
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.24006
Subject(s) - metabotropic glutamate receptor 5 , astrocyte , metabotropic glutamate receptor , adenosine , biology , glutamate receptor , metabotropic glutamate receptor 3 , adenosine a1 receptor , metabotropic glutamate receptor 6 , adenosine a2b receptor , metabotropic receptor , microbiology and biotechnology , adenosine a3 receptor , metabotropic glutamate receptor 8 , purinergic signalling , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 7 , adenosine receptor , neuroscience , agonist , receptor , endocrinology , biochemistry , central nervous system
Metabotropic glutamate receptor 5 (mGluR5) in astrocytes is a key molecule for controlling synapse remodeling. Although mGluR5 is abundant in neonatal astrocytes, its level is gradually down‐regulated during development and is almost absent in the adult. However, in several pathological conditions, mGluR5 re‐emerges in adult astrocytes and contributes to disease pathogenesis by forming uncontrolled synapses. Thus, controlling mGluR5 expression in astrocyte is critical for several diseases, but the mechanism that regulates mGluR5 expression remains unknown. Here, we show that adenosine triphosphate (ATP)/adenosine‐mediated signals down‐regulate mGluR5 in astrocytes. First, in situ Ca 2+ imaging of astrocytes in acute cerebral slices from post‐natal day (P)7‐P28 mice showed that Ca 2+ responses evoked by (S)‐3,5‐dihydroxyphenylglycine (DHPG), a mGluR5 agonist, decreased during development, whereas those evoked by ATP or its metabolite, adenosine, increased. Second, ATP and adenosine suppressed expression of the mGluR5 gene, Grm5 , in cultured astrocytes. Third, the decrease in the DHPG‐evoked Ca 2+ responses was associated with down‐regulation of Grm5 . Interestingly, among several adenosine (P1) receptor and ATP (P2) receptor genes, only the adenosine A 2B receptor gene, Adora2b , was up‐regulated in the course of development. Indeed, we observed that down‐regulation of Grm5 was suppressed in Adora2b knockout astrocytes at P14 and in situ Ca 2+ imaging from Adora2b knockout mice indicated that the A 2B receptor inhibits mGluR5 expression in astrocytes. Furthermore, deletion of A 2B receptor increased the number of excitatory synapse in developmental stage. Taken together, the A 2B receptor is critical for down‐regulation of mGluR5 in astrocytes, which would contribute to terminate excess synaptogenesis during development.