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

Publication date: 13 February 2018
Source:Cell Reports, Volume 22, Issue 7
Author(s): Sarah J. Parkhurst, Pratik Adhikari, Jovana S. Navarrete, Arièle Legendre, Miguel Manansala, Fred W. Wolf
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.

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Teaser

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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