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- Mansouri, M., et al.
(författare)
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Autistic-like behaviours and associated brain structural plasticity are modulated by oxytocin in maternally separated rats
- 2020
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328. ; 393:September
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early psycho-social experiences influence the developing brain and possible onset of various neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD). ASD is characterized by a variety of brain abnormalities, including alteration of oxytocin receptors in the brain. Recently, early life adverse experiences, such as maternal separation (MS), have been shown to constitute risk factors for ASD in preclinical studies. Therefore, the main aims of the current study were to i) explore the association between onset of autistic-like behaviours and molecular/structural changes in the brain following MS, and ii) evaluate the possible beneficial effects of oxytocin treatment on the same parameters. Method and Material: Male rats were exposed to the maternal separation from post-natal day (PND) 1 to PND14. After weaning, daily injections of oxytocin (1 mg/kg, ip) were administered (PND 22-30), followed by examination of autism-related behaviours at adolescence (PND 42-50). Brain structural plasticity was examined using stereological methods, and the plasma level of brain derived neurotrophic factor (BDNF) was analysed using ELISA. Results: We found that maternal separation induced autistic-like behaviours, which was associated with increase in the hippocampal CA1 stratum radiatum (CA1.SR) volume. In addition, we observed increase in the infralimbic brain region volume and in the number of the pyramidal neurons in the same brain region. Maternal separation significantly increased the plasma BDNF levels. Treatment with oxytocin improved autistic like behaviours, normalized the number of neurons and the volume of the infralimbic region as well as the plasma BDNF level (p < 0.05). Conclusion: Maternal separation induced autistic-like behaviours, brain structural impairment together with plasma BDNF level abnormally, which could be improved by oxytocin treatment.
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| 2. |
- Mansouri, M., et al.
(författare)
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Dual Profile of Environmental Enrichment and Autistic-Like Behaviors in the Maternal Separated Model in Rats
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 22:3
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Tidskriftsartikel (refereegranskat)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, 3 h/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.
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| 3. |
- Mansouri, M., et al.
(författare)
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Excessive audio-visual stimulation leads to impaired social behavior with an effect on amygdala: Early life excessive exposure to digital devices in male rats
- 2022
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 56:12, s. 6174-6186
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Tidskriftsartikel (refereegranskat)abstract
- Today, the effect of extreme early-life exposure to digital devices is suggested as a risk factor for neurodevelopmental disorders. However, the multitudes of factors that influence brain development with subsequent behavioral abnormality have not been fully elucidated. Herein, we simulated extreme early-life exposure to digital devices in rat by audio and visual stimulation and investigated its effects on autism-related behaviors and brain structural alteration. Male rat pups were exposed to excessive audio-visual stimulation (EAVS) from PND (post-natal day) 12 to PND 35, with and without maternal separation (MS). Autism related behaviors including abnormal sociability, stereotype behaviors, anxiety and locomotor dysfunction were tested at PND 42. Brain structural alternation was examined by considering amygdala, mPFC (medial prefrontal cortex) and hippocampal regions with performing 3D quantitative stereological analysis. We found that EAVS led to social behavior deficit and higher locomotion in rats which were associated with increased in number of the neurons and volume of the amygdala. We also showed that MS did not exaggerate the effect of extreme sensory stimulation on behavior and structure of brain. This study proposed EAVS in rats as an animal model of early exposure to digital devices for investigating possible neurobiological alternations underlying autistic-like behaviors with emphasis on the amygdala area.
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