Monireh Mansouri1,2,3, Hamidreza Pouretemad1,4, Gregers Wegener2,5,6, Mehrdad Roghani7, Masoud Afshari1, Carina Mallard8, Maryam Ardalan2,8. 1. Department of Cognitive Psychology, Institute for Cognitive and Brain Sciences, Shahid Beheshti University, Tehran 1983969411, Iran. 2. Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark. 3. Center of Excellence in Cognitive Neuropsychology, Institute for Cognitive and Brain Sciences, Shahid Beheshti University, Tehran 1983969411, Iran. 4. Department of Psychology, Shahid Beheshti University, Tehran 1983969411, Iran. 5. Center of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa. 6. AUGUST Centre, Department of Clinical Medicine, Aarhus University, 8240 Risskov, Denmark. 7. Neurophysiology Research Center, Shahed University, Tehran 3319118651, Iran. 8. Centre for Perinatal Medicine and Health, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 50530 Gothenburg, Sweden.
Abstract
BACKGROUND: Environmental Enrichment (EE) has been suggested as a possible therapeutic intervention for neurodevelopmental disorders such as autism. Although the benefits of this therapeutic method have been reported in some animal models and human studies, the unknown pathophysiology of autism as well as number of conflicting results, urge for further examination of the therapeutic potential of EE in autism. Therefore, the aim of this study was to examine the effects of environmental enrichment on autism-related behaviors which were induced in the maternal separation (MS) animal model. MATERIAL AND METHODS: Maternally separated (post-natal day (PND) 1-14, 3h/day) and control male rats were at weaning (PND21) age equally divided into rats housed in enriched environment and normal environment. At adolescence (PND42-50), the four groups were behaviorally tested for direct social interaction, sociability, repetitive behaviors, anxiety behavior, and locomotion. Following completion of the behavioral tests, the blood and brain tissue samples were harvested in order to assess plasma level of brain derived neurotrophic factor (BDNF) and structural plasticity of brain using ELISA and stereological methods respectively. RESULTS: We found that environmental enrichment reduced repetitive behaviors but failed to improve the impaired sociability and anxiety behaviors which were induced by maternal separation. Indeed, EE exacerbated anxiety and social behaviors deficits in association with increased plasma BDNF level, larger volume of the hippocampus and infra-limbic region and higher number of neurons in the infra-limbic area (p < 0.05). Conclusion: We conclude that environmental enrichment has a significant improvement effect on the repetitive behavior as one of the core autistic-like behaviors induced by maternal separation but has negative effect on the anxiety and social behaviors which might have been modulated by BDNF.
BACKGROUND: Environmental Enrichment (EE) has been suggested as a possible therapeutic intervention for neurodevelopmental disorders such as autism. Although the benefits of this therapeutic method have been reported in some animal models and human studies, the unknown pathophysiology of autism as well as number of conflicting results, urge for further examination of the therapeutic potential of EE in autism. Therefore, the aim of this study was to examine the effects of environmental enrichment on autism-related behaviors which were induced in the maternal separation (MS) animal model. MATERIAL AND METHODS: Maternally separated (post-natal day (PND) 1-14, 3h/day) and control male rats were at weaning (PND21) age equally divided into rats housed in enriched environment and normal environment. At adolescence (PND42-50), the four groups were behaviorally tested for direct social interaction, sociability, repetitive behaviors, anxiety behavior, and locomotion. Following completion of the behavioral tests, the blood and brain tissue samples were harvested in order to assess plasma level of brain derived neurotrophic factor (BDNF) and structural plasticity of brain using ELISA and stereological methods respectively. RESULTS: We found that environmental enrichment reduced repetitive behaviors but failed to improve the impaired sociability and anxiety behaviors which were induced by maternal separation. Indeed, EE exacerbated anxiety and social behaviors deficits in association with increased plasma BDNF level, larger volume of the hippocampus and infra-limbic region and higher number of neurons in the infra-limbic area (p < 0.05). Conclusion: We conclude that environmental enrichment has a significant improvement effect on the repetitive behavior as one of the core autistic-like behaviors induced by maternal separation but has negative effect on the anxiety and social behaviors which might have been modulated by BDNF.
Entities:
Keywords:
BDNF; animal model of autism; brain plasticity; environmental enrichment; neonatal isolation
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