Decreased Hippocampal Neuroplasticity and Behavioral Impairment in an Animal Model of Inhalant Abuse
Thinners are highly toxic chemicals widely employed as organic solvents in industrial and domestic use. They have psychoactive properties when inhaled, and their chronic abuse as inhalants is associated with severe long-term health effects, including brain damage and cognitive-behavioral alterations...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnins.2018.00035/full |
| _version_ | 1811342250048749568 |
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| author | Hanaa Malloul Mohammed Bennis Sara Bonzano Sara Bonzano Giovanna Gambarotta Isabelle Perroteau Silvia De Marchis Silvia De Marchis Saadia Ba-M'hamed |
| author_facet | Hanaa Malloul Mohammed Bennis Sara Bonzano Sara Bonzano Giovanna Gambarotta Isabelle Perroteau Silvia De Marchis Silvia De Marchis Saadia Ba-M'hamed |
| author_sort | Hanaa Malloul |
| collection | DOAJ |
| description | Thinners are highly toxic chemicals widely employed as organic solvents in industrial and domestic use. They have psychoactive properties when inhaled, and their chronic abuse as inhalants is associated with severe long-term health effects, including brain damage and cognitive-behavioral alterations. Yet, the sites and mechanisms of action of these compounds on the brain are far from being fully understood. Here, we investigated the consequences of paint thinner inhalation in adult male mice. Depression-like behaviors and an anxiolytic effect were found following repeated exposure in chronic treatments lasting 12 weeks. Both subchronic (6 weeks) and chronic treatments impaired learning and memory functions, while no changes were observed after acute treatment. To investigate possible molecular/structural alterations underlying such behavioral changes, we focused on the hippocampus. Notably, prolonged, but not acute thinner inhalation strongly affected adult neurogenesis in the dentate gyrus (DG), reducing progenitor cell proliferation after chronic treatments and impairing the survival of newborn neurons following both chronic and subchronic treatments. Furthermore, a down-regulation in the expression of BDNF and NMDA receptor subunits as well as a reduction in CREB expression/phosphorylation were found in the hippocampi of chronically treated mice. Our findings demonstrate for the first time significant structural and molecular changes in the adult hippocampus after prolonged paint thinner inhalation, indicating reduced hippocampal neuroplasticity and strongly supporting its implication in the behavioral dysfunctions associated to inhalant abuse. |
| first_indexed | 2024-04-13T19:08:20Z |
| format | Article |
| id | doaj.art-9b37d8df1f424a6194afc389ce19e7d3 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-13T19:08:20Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-9b37d8df1f424a6194afc389ce19e7d32022-12-22T02:33:55ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-02-011210.3389/fnins.2018.00035324896Decreased Hippocampal Neuroplasticity and Behavioral Impairment in an Animal Model of Inhalant AbuseHanaa Malloul0Mohammed Bennis1Sara Bonzano2Sara Bonzano3Giovanna Gambarotta4Isabelle Perroteau5Silvia De Marchis6Silvia De Marchis7Saadia Ba-M'hamed8Laboratory of Pharmacology, Neurobiology and Behavior (URAC-37), Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakech, MoroccoLaboratory of Pharmacology, Neurobiology and Behavior (URAC-37), Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakech, MoroccoDepartment of Life Sciences and Systems Biology, University of Turin, Turin, ItalyNeuroscience Institute Cavalieri Ottolenghi, Orbassano, ItalyDepartment of Clinical and Biological Sciences, University of Turin, Orbassano, ItalyDepartment of Clinical and Biological Sciences, University of Turin, Orbassano, ItalyDepartment of Life Sciences and Systems Biology, University of Turin, Turin, ItalyNeuroscience Institute Cavalieri Ottolenghi, Orbassano, ItalyLaboratory of Pharmacology, Neurobiology and Behavior (URAC-37), Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakech, MoroccoThinners are highly toxic chemicals widely employed as organic solvents in industrial and domestic use. They have psychoactive properties when inhaled, and their chronic abuse as inhalants is associated with severe long-term health effects, including brain damage and cognitive-behavioral alterations. Yet, the sites and mechanisms of action of these compounds on the brain are far from being fully understood. Here, we investigated the consequences of paint thinner inhalation in adult male mice. Depression-like behaviors and an anxiolytic effect were found following repeated exposure in chronic treatments lasting 12 weeks. Both subchronic (6 weeks) and chronic treatments impaired learning and memory functions, while no changes were observed after acute treatment. To investigate possible molecular/structural alterations underlying such behavioral changes, we focused on the hippocampus. Notably, prolonged, but not acute thinner inhalation strongly affected adult neurogenesis in the dentate gyrus (DG), reducing progenitor cell proliferation after chronic treatments and impairing the survival of newborn neurons following both chronic and subchronic treatments. Furthermore, a down-regulation in the expression of BDNF and NMDA receptor subunits as well as a reduction in CREB expression/phosphorylation were found in the hippocampi of chronically treated mice. Our findings demonstrate for the first time significant structural and molecular changes in the adult hippocampus after prolonged paint thinner inhalation, indicating reduced hippocampal neuroplasticity and strongly supporting its implication in the behavioral dysfunctions associated to inhalant abuse.http://journal.frontiersin.org/article/10.3389/fnins.2018.00035/fullthinner inhalationdepressionanxietycognitive impairmentDG neurogenesisBDNF |
| spellingShingle | Hanaa Malloul Mohammed Bennis Sara Bonzano Sara Bonzano Giovanna Gambarotta Isabelle Perroteau Silvia De Marchis Silvia De Marchis Saadia Ba-M'hamed Decreased Hippocampal Neuroplasticity and Behavioral Impairment in an Animal Model of Inhalant Abuse Frontiers in Neuroscience thinner inhalation depression anxiety cognitive impairment DG neurogenesis BDNF |
| title | Decreased Hippocampal Neuroplasticity and Behavioral Impairment in an Animal Model of Inhalant Abuse |
| title_full | Decreased Hippocampal Neuroplasticity and Behavioral Impairment in an Animal Model of Inhalant Abuse |
| title_fullStr | Decreased Hippocampal Neuroplasticity and Behavioral Impairment in an Animal Model of Inhalant Abuse |
| title_full_unstemmed | Decreased Hippocampal Neuroplasticity and Behavioral Impairment in an Animal Model of Inhalant Abuse |
| title_short | Decreased Hippocampal Neuroplasticity and Behavioral Impairment in an Animal Model of Inhalant Abuse |
| title_sort | decreased hippocampal neuroplasticity and behavioral impairment in an animal model of inhalant abuse |
| topic | thinner inhalation depression anxiety cognitive impairment DG neurogenesis BDNF |
| url | http://journal.frontiersin.org/article/10.3389/fnins.2018.00035/full |
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