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MORPHINE MODULATION OF THROMBSPONDIN LEVELS IN ASTROCYTES AND ITS IMPLICATIONS FOR SYNAPSE FORMATION
Author(s) -
Coscia Carmine James,
Ikeda Hiroko,
Miyatake Mayumi,
Koshikawa Noriaki,
Ochiai Kuniyasu,
Yamada Kiyoshi,
Kiss Alexi,
Donlin Maureen,
Panneton W. Michael,
Churchill James,
Green Michael,
Siddiqui Akbar,
Leinweber Andrew,
Ezerskiy Luba,
Rendell Victoria,
Belcheva Mariana
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.710.2
Subject(s) - mapk/erk pathway , astrocyte , synapse , nucleus accumbens , neuroscience , chemistry , microbiology and biotechnology , phosphorylation , biology , central nervous system
Opioid receptor signaling via the ERK/MAP kinase phosphorylation cascade initiates diverse cellular responses that are cell type dependent. In astrocytes, multiple μ opioid receptor mediated mechanisms of ERK activation exist that are temporally distinctive and feature different outcomes. Upon discovering that chronic opiate treatment of rats followed by spontaneous withdrawal down regulates thrombospondin1 (TSP1) expression in the nucleus accumbens and cortex, we investigated the mechanism of action of this modulation in astrocytes. TSP1 is synthesized in astrocytes and released into the extracellular matrix where it plays a role in synapse formation. Acute morphine (h) reduced TSP1 protein levels in astrocytes by an ERK dependent mechanism. Chronic (days) opiates repressed expression of TSP1 and reduced its protein levels. Morphine reduced TSP1 levels stimulated by TGFβ1. Accordingly, chronic morphine treatment of astrocyte neuron co‐cultures reduced neurite outgrowth and synapse formation. Taken together our results suggest that inhibitory actions of morphine on TSP1 and synapse formation entail multiple temporally distinctive mechanisms. Supported by DA005412.