Perineurial Barrier Glia Physically Respond to Alcohol in an Akap200-Dependent Manner to Promote Tolerance
Summary: 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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-02-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718300810 |
| _version_ | 1818314325045018624 |
|---|---|
| author | Sarah J. Parkhurst Pratik Adhikari Jovana S. Navarrete Arièle Legendre Miguel Manansala Fred W. Wolf |
| author_facet | Sarah J. Parkhurst Pratik Adhikari Jovana S. Navarrete Arièle Legendre Miguel Manansala Fred W. Wolf |
| author_sort | Sarah J. Parkhurst |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-13T08:47:50Z |
| format | Article |
| id | doaj.art-c2ac2f31e4ea4c6cb31f86e682876181 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T08:47:50Z |
| publishDate | 2018-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c2ac2f31e4ea4c6cb31f86e6828761812022-12-21T23:53:26ZengElsevierCell Reports2211-12472018-02-012271647165610.1016/j.celrep.2018.01.049Perineurial Barrier Glia Physically Respond to Alcohol in an Akap200-Dependent Manner to Promote ToleranceSarah J. Parkhurst0Pratik Adhikari1Jovana S. Navarrete2Arièle Legendre3Miguel Manansala4Fred W. Wolf5Quantitative and Systems Biology Graduate Program, University of California, Merced, CA 95343, USAQuantitative and Systems Biology Graduate Program, University of California, Merced, CA 95343, USAMolecular Cell Biology, School of Natural Sciences, University of California, Merced, CA 95343, USAMolecular Cell Biology, School of Natural Sciences, University of California, Merced, CA 95343, USAMolecular Cell Biology, School of Natural Sciences, University of California, Merced, CA 95343, USAQuantitative and Systems Biology Graduate Program, University of California, Merced, CA 95343, USA; Molecular Cell Biology, School of Natural Sciences, University of California, Merced, CA 95343, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124718300810ethanoladdictionblood-brain barrierA kinase anchoring proteinPKAcalcium signaling |
| spellingShingle | Sarah J. Parkhurst Pratik Adhikari Jovana S. Navarrete Arièle Legendre Miguel Manansala Fred W. Wolf Perineurial Barrier Glia Physically Respond to Alcohol in an Akap200-Dependent Manner to Promote Tolerance Cell Reports ethanol addiction blood-brain barrier A kinase anchoring protein PKA calcium signaling |
| title | Perineurial Barrier Glia Physically Respond to Alcohol in an Akap200-Dependent Manner to Promote Tolerance |
| title_full | Perineurial Barrier Glia Physically Respond to Alcohol in an Akap200-Dependent Manner to Promote Tolerance |
| title_fullStr | Perineurial Barrier Glia Physically Respond to Alcohol in an Akap200-Dependent Manner to Promote Tolerance |
| title_full_unstemmed | Perineurial Barrier Glia Physically Respond to Alcohol in an Akap200-Dependent Manner to Promote Tolerance |
| title_short | Perineurial Barrier Glia Physically Respond to Alcohol in an Akap200-Dependent Manner to Promote Tolerance |
| title_sort | perineurial barrier glia physically respond to alcohol in an akap200 dependent manner to promote tolerance |
| topic | ethanol addiction blood-brain barrier A kinase anchoring protein PKA calcium signaling |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718300810 |
| work_keys_str_mv | AT sarahjparkhurst perineurialbarriergliaphysicallyrespondtoalcoholinanakap200dependentmannertopromotetolerance AT pratikadhikari perineurialbarriergliaphysicallyrespondtoalcoholinanakap200dependentmannertopromotetolerance AT jovanasnavarrete perineurialbarriergliaphysicallyrespondtoalcoholinanakap200dependentmannertopromotetolerance AT arielelegendre perineurialbarriergliaphysicallyrespondtoalcoholinanakap200dependentmannertopromotetolerance AT miguelmanansala perineurialbarriergliaphysicallyrespondtoalcoholinanakap200dependentmannertopromotetolerance AT fredwwolf perineurialbarriergliaphysicallyrespondtoalcoholinanakap200dependentmannertopromotetolerance |