title: Environmental enrichment increases doublecortin-associated new neurons and decreases neuronal death without modifying anxiety-like behavior in mice chronically exposed to toluene.
abstract: Toluene misuse is a health problem worldwide with broad effects at the level of the central nervous system; however, therapeutic alternatives for inhalant abusers are limited. Chronic use of volatile substances is associated with different neurological and cognitive alterations, being anxiety a psychiatric condition with high prevalence. At cellular level toluene reduces neurogenesis and induces neuronal death. On the other hand, environmental enrichment has demonstrated to produce positive effects at behavioral and neuronal levels. Thus, the aim of the present work was to model alterations occasioned after repeated exposure to toluene (anxiety, reduction in neurogenesis - measured as doublecortin-labeled cells - and neuronal death). Subsequently, the influence of environmental enrichment on these effects was evaluated. Adolescent mice were exposed to toluene vapors from 1 to 4 weeks. Effects on anxiety were evaluated with the burying behavior test, whereas neurogenesis and hippocampal cell death were analyzed with immunohistochemistry, using anti-doublecortin or anti-active-Caspase-3 antibodies, respectively. Results showed that chronic toluene exposure increased anxiety in the burying behavior test; additionally, toluene decreased neurogenesis and enhanced neuronal death. Environmental enrichment (EE) enhanced the anxiety like response in air-exposed mice but did not modify the toluene anxiety response. Additionally, EE enhanced neurogenesis in toluene-pretreated animals at the same level to that found in animals unexposed to toluene and decreased neuronal death. Overall, the present study showed that environmental enrichment positively impacts some effects produced by repeated exposure to toluene.
authors.affiliation: Sección de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Col. Santo Tomás, Mexico, CP 11340, Mexico; Laboratorio Integrativo para el Estudio de Sustancias Inhalables Adictivas, Dirección de Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, Mexico, CP 14370, Mexico. Electronic address: nayepam@yahoo.com.mx.
authors.forename: Nayeli
authors.initials: N
authors.lastname: Paez-Martinez
authors.forename: Zoraida
authors.initials: Z
authors.lastname: Flores-Serrano
authors.forename: Leonardo
authors.initials: L
authors.lastname: Ortiz-Lopez
authors.forename: Gerardo
authors.initials: G
authors.lastname: Ramirez-Rodriguez
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D000089622:Doublecortin Domain Proteins; D004777:Environment; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D014050:Toluene / Q000633:toxicity*
chemical_list: D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D014050:Toluene
keywords: Anxiety; Doublecortin; Environmental enrichment; Neurogenesis; Neuronal death; Toluene