The Matricellular Protein Hevin Is Involved in Alcohol Use Disorder
Astrocytic-secreted matricellular proteins have been shown to influence various aspects of synaptic function. More recently, they have been found altered in animal models of psychiatric disorders such as drug addiction. Hevin (also known as Sparc-like 1) is a matricellular protein highly expressed i...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/2/234 |
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| author | Amaia Nuñez-delMoral Paula C. Bianchi Iria Brocos-Mosquera Augusto Anesio Paola Palombo Rosana Camarini Fabio C. Cruz Luis F. Callado Vincent Vialou Amaia M. Erdozain |
| author_facet | Amaia Nuñez-delMoral Paula C. Bianchi Iria Brocos-Mosquera Augusto Anesio Paola Palombo Rosana Camarini Fabio C. Cruz Luis F. Callado Vincent Vialou Amaia M. Erdozain |
| author_sort | Amaia Nuñez-delMoral |
| collection | DOAJ |
| description | Astrocytic-secreted matricellular proteins have been shown to influence various aspects of synaptic function. More recently, they have been found altered in animal models of psychiatric disorders such as drug addiction. Hevin (also known as Sparc-like 1) is a matricellular protein highly expressed in the adult brain that has been implicated in resilience to stress, suggesting a role in motivated behaviors. To address the possible role of hevin in drug addiction, we quantified its expression in human postmortem brains and in animal models of alcohol abuse. Hevin mRNA and protein expression were analyzed in the postmortem human brain of subjects with an antemortem diagnosis of alcohol use disorder (AUD, <i>n</i> = 25) and controls (<i>n</i> = 25). All the studied brain regions (prefrontal cortex, hippocampus, caudate nucleus and cerebellum) in AUD subjects showed an increase in hevin levels either at mRNA or/and protein levels. To test if this alteration was the result of alcohol exposure or indicative of a susceptibility factor to alcohol consumption, mice were exposed to different regimens of intraperitoneal alcohol administration. Hevin protein expression was increased in the nucleus accumbens after withdrawal followed by a ethanol challenge. The role of hevin in AUD was determined using an RNA interference strategy to downregulate hevin expression in nucleus accumbens astrocytes, which led to increased ethanol consumption. Additionally, ethanol challenge after withdrawal increased hevin levels in blood plasma. Altogether, these results support a novel role for hevin in the neurobiology of AUD. |
| first_indexed | 2024-03-11T09:06:24Z |
| format | Article |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T09:06:24Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-df1311d0f5384142a20fc43cc32959b22023-11-16T19:22:15ZengMDPI AGBiomolecules2218-273X2023-01-0113223410.3390/biom13020234The Matricellular Protein Hevin Is Involved in Alcohol Use DisorderAmaia Nuñez-delMoral0Paula C. Bianchi1Iria Brocos-Mosquera2Augusto Anesio3Paola Palombo4Rosana Camarini5Fabio C. Cruz6Luis F. Callado7Vincent Vialou8Amaia M. Erdozain9Department of Pharmacology, University of the Basque Country, UPV/EHU, 48940 Leioa, SpainDepartment of Pharmacology, Universidade Federal de São Paulo-UNIFESP, São Paulo 04023-062, BrazilDepartment of Pharmacology, University of the Basque Country, UPV/EHU, 48940 Leioa, SpainDepartment of Pharmacology, Universidade Federal de São Paulo-UNIFESP, São Paulo 04023-062, BrazilDepartment of Pharmacology, Universidade Federal de São Paulo-UNIFESP, São Paulo 04023-062, BrazilDepartment of Pharmacology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, BrazilDepartment of Pharmacology, Universidade Federal de São Paulo-UNIFESP, São Paulo 04023-062, BrazilDepartment of Pharmacology, University of the Basque Country, UPV/EHU, 48940 Leioa, SpainInstitute of Biology Paris Seine, Neuroscience Paris Seine, CNRS UMR8246, INSERM U1130, Sorbonne Université, 75005 Paris, FranceDepartment of Pharmacology, University of the Basque Country, UPV/EHU, 48940 Leioa, SpainAstrocytic-secreted matricellular proteins have been shown to influence various aspects of synaptic function. More recently, they have been found altered in animal models of psychiatric disorders such as drug addiction. Hevin (also known as Sparc-like 1) is a matricellular protein highly expressed in the adult brain that has been implicated in resilience to stress, suggesting a role in motivated behaviors. To address the possible role of hevin in drug addiction, we quantified its expression in human postmortem brains and in animal models of alcohol abuse. Hevin mRNA and protein expression were analyzed in the postmortem human brain of subjects with an antemortem diagnosis of alcohol use disorder (AUD, <i>n</i> = 25) and controls (<i>n</i> = 25). All the studied brain regions (prefrontal cortex, hippocampus, caudate nucleus and cerebellum) in AUD subjects showed an increase in hevin levels either at mRNA or/and protein levels. To test if this alteration was the result of alcohol exposure or indicative of a susceptibility factor to alcohol consumption, mice were exposed to different regimens of intraperitoneal alcohol administration. Hevin protein expression was increased in the nucleus accumbens after withdrawal followed by a ethanol challenge. The role of hevin in AUD was determined using an RNA interference strategy to downregulate hevin expression in nucleus accumbens astrocytes, which led to increased ethanol consumption. Additionally, ethanol challenge after withdrawal increased hevin levels in blood plasma. Altogether, these results support a novel role for hevin in the neurobiology of AUD.https://www.mdpi.com/2218-273X/13/2/234hevinastrocytesalcohol use disorderhuman post-mortem brainSparcl1 |
| spellingShingle | Amaia Nuñez-delMoral Paula C. Bianchi Iria Brocos-Mosquera Augusto Anesio Paola Palombo Rosana Camarini Fabio C. Cruz Luis F. Callado Vincent Vialou Amaia M. Erdozain The Matricellular Protein Hevin Is Involved in Alcohol Use Disorder Biomolecules hevin astrocytes alcohol use disorder human post-mortem brain Sparcl1 |
| title | The Matricellular Protein Hevin Is Involved in Alcohol Use Disorder |
| title_full | The Matricellular Protein Hevin Is Involved in Alcohol Use Disorder |
| title_fullStr | The Matricellular Protein Hevin Is Involved in Alcohol Use Disorder |
| title_full_unstemmed | The Matricellular Protein Hevin Is Involved in Alcohol Use Disorder |
| title_short | The Matricellular Protein Hevin Is Involved in Alcohol Use Disorder |
| title_sort | matricellular protein hevin is involved in alcohol use disorder |
| topic | hevin astrocytes alcohol use disorder human post-mortem brain Sparcl1 |
| url | https://www.mdpi.com/2218-273X/13/2/234 |
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