Perineurial Barrier Glia Physically Respond to Alcohol in an Akap200-Dependent Manner to Promote Tolerance.

Perineurial Barrier Glia Physically Respond to Alcohol in an Akap200-Dependent Manner to Promote Tolerance.
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DOI:
10.1016/j.celrep.2018.01.049
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发表时间:
2018-02-13
期刊:
影响因子:
8.8
通讯作者:
Wolf FW
Wolf FW
中科院分区:
生物学1区
文献类型:
--
作者:
Parkhurst SJ;Adhikari P;Navarrete JS;Legendre A;Manansala M;Wolf FW

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Ethanol is the most common drug of abuse. It exerts its behavioral effects by acting on widespread neural circuits; however, its impact on glial cells is less understood. We show that Drosophila perineurial glia are critical for ethanol tolerance, a simple form of behavioral plasticity. The perineurial glia form the continuous outer cellular layer of the blood-brain barrier and are the interface between the brain and the circulation. Ethanol tolerance development requires the A kinase anchoring protein Akap200 specifically in perineurial glia. Akap200 tightly coordinates protein kinase A, actin, and calcium signaling at the membrane to control tolerance. Furthermore, ethanol causes a structural remodeling of the actin cytoskeleton and perineurial membrane topology in an Akap200-dependent manner, without disrupting classical barrier functions. Our findings reveal an active molecular signaling process in the cells at the blood-brain interface that permits a form of behavioral plasticity induced by ethanol. Parkhurst et. al show that glia at the interface of the Drosophila circulation and brain change shape in response to alcohol and permit the development of alcohol tolerance. This depends on the anchoring of signaling molecules to the plasma membrane in proximity to the actin cytoskeleton.
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