小胶质细胞
NMDA受体
脑源性神经营养因子
医学
类阿片
吗啡
药理学
导水管周围灰质
米诺环素
受体
神经营养因子
神经科学
化学
内科学
生物
中枢神经系统
炎症
中脑
抗生素
生物化学
作者
Yosuke Matsushita,Idowu Olaposi Omotuyi,Takehiro Mukae,Hiroshi Ueda
标识
DOI:10.2174/138161281942140105161733
摘要
Herein, we investigated the role of periaqueductal gray (PAG)-resident microglia in the development of morphine tolerance and its underlying mechanisms. We showed that clodronate and minocycline known as microglia inhibitors reversed morphine tolerance, providing proof that microglia activation has key role in the development of morphine tolerance. The microglia-mediated anti-opioid mechanism occurs via sequential BDNF release and NMDA expression. Experimental evidence is provided here as conditional bdnf knockout mice (bdnf⁻/⁻) failed to develop tolerance following Cre-recombinase adenovirus treatment. Increased BDNF expression followed microglia activation in acute minocycline treatment reversible manner. Following BDNF release, NR2A subunit of NMDA receptor was upregulated in anti-BDNF reversible manner showing the contribution of BDNF signaling in the control of NMDA receptor expression following chronic morphine treatment. Our data provide compelling evidence that microglia activation and BDNF release are key regulators in opioid tolerance mechanism via glutaminergic synapse plasticity.
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