Possible role of NO/NMDA pathway in the autistic-like behaviors induced by maternal separation stress in mice.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Maternal separation (MS) stress is an established model of early-life stress associated with autistic-like behaviors. Altered glutamatergic and nitrergic neurotransmissions may contribute to the pathophysiology of ASD. However,...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0292631 |
| _version_ | 1827793627376517120 |
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| author | Fatemeh Khaledi Hossein Tahmasebi Dehkordi Elham Zarean Mehrdad Shahrani Hossein Amini-Khoei |
| author_facet | Fatemeh Khaledi Hossein Tahmasebi Dehkordi Elham Zarean Mehrdad Shahrani Hossein Amini-Khoei |
| author_sort | Fatemeh Khaledi |
| collection | DOAJ |
| description | Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Maternal separation (MS) stress is an established model of early-life stress associated with autistic-like behaviors. Altered glutamatergic and nitrergic neurotransmissions may contribute to the pathophysiology of ASD. However, the specific mechanisms underlying these alterations and their relationship to MS-induced autistic-like behaviors remain unclear. Addressing this knowledge gap, this study aims to elucidate the involvement of the nitric oxide (NO)/ N-methyl-D-aspartate (NMDA) pathway in MS-induced autistic-like behaviors in mice. This knowledge has the potential to guide future research, potentially leading to the development of targeted interventions or treatments aimed at modulating the NO/NMDA pathway to ameliorate ASD symptoms. Ninety male Naval Medical Research Institute (NMRI) mice were assigned to six groups (n = 15) comprising a control group (treated with saline) and five groups subjected to MS and treated with saline, ketamine, NMDA, L-NAME, and L-arginine. Behavioral tests were conducted, including the three-chamber test, shuttle box, elevated plus-maze, and marble burying test. Gene expression of iNOS, nNOS, and NMDA-R subunits (NR2A and NR2B), along with nitrite levels, was evaluated in the hippocampus. The findings demonstrated that MS induced autistic-like behaviors, accompanied by increased gene expression of iNOS, nNOS, NR2B, NR2A, and elevated nitrite levels in the hippocampus. Modulation of the NO/NMDA pathway with activators and inhibitors altered the effects of MS. These results suggest that the NO/NMDA pathway plays a role in mediating the negative effects of MS and potentially contributes to the development of autistic-like behaviors in maternally separated mice. |
| first_indexed | 2024-03-11T18:22:11Z |
| format | Article |
| id | doaj.art-76cdfc7336d2426daa9260ab2b1fb75f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-11T18:22:11Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-76cdfc7336d2426daa9260ab2b1fb75f2023-10-15T05:32:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-011810e029263110.1371/journal.pone.0292631Possible role of NO/NMDA pathway in the autistic-like behaviors induced by maternal separation stress in mice.Fatemeh KhalediHossein Tahmasebi DehkordiElham ZareanMehrdad ShahraniHossein Amini-KhoeiAutism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Maternal separation (MS) stress is an established model of early-life stress associated with autistic-like behaviors. Altered glutamatergic and nitrergic neurotransmissions may contribute to the pathophysiology of ASD. However, the specific mechanisms underlying these alterations and their relationship to MS-induced autistic-like behaviors remain unclear. Addressing this knowledge gap, this study aims to elucidate the involvement of the nitric oxide (NO)/ N-methyl-D-aspartate (NMDA) pathway in MS-induced autistic-like behaviors in mice. This knowledge has the potential to guide future research, potentially leading to the development of targeted interventions or treatments aimed at modulating the NO/NMDA pathway to ameliorate ASD symptoms. Ninety male Naval Medical Research Institute (NMRI) mice were assigned to six groups (n = 15) comprising a control group (treated with saline) and five groups subjected to MS and treated with saline, ketamine, NMDA, L-NAME, and L-arginine. Behavioral tests were conducted, including the three-chamber test, shuttle box, elevated plus-maze, and marble burying test. Gene expression of iNOS, nNOS, and NMDA-R subunits (NR2A and NR2B), along with nitrite levels, was evaluated in the hippocampus. The findings demonstrated that MS induced autistic-like behaviors, accompanied by increased gene expression of iNOS, nNOS, NR2B, NR2A, and elevated nitrite levels in the hippocampus. Modulation of the NO/NMDA pathway with activators and inhibitors altered the effects of MS. These results suggest that the NO/NMDA pathway plays a role in mediating the negative effects of MS and potentially contributes to the development of autistic-like behaviors in maternally separated mice.https://doi.org/10.1371/journal.pone.0292631 |
| spellingShingle | Fatemeh Khaledi Hossein Tahmasebi Dehkordi Elham Zarean Mehrdad Shahrani Hossein Amini-Khoei Possible role of NO/NMDA pathway in the autistic-like behaviors induced by maternal separation stress in mice. PLoS ONE |
| title | Possible role of NO/NMDA pathway in the autistic-like behaviors induced by maternal separation stress in mice. |
| title_full | Possible role of NO/NMDA pathway in the autistic-like behaviors induced by maternal separation stress in mice. |
| title_fullStr | Possible role of NO/NMDA pathway in the autistic-like behaviors induced by maternal separation stress in mice. |
| title_full_unstemmed | Possible role of NO/NMDA pathway in the autistic-like behaviors induced by maternal separation stress in mice. |
| title_short | Possible role of NO/NMDA pathway in the autistic-like behaviors induced by maternal separation stress in mice. |
| title_sort | possible role of no nmda pathway in the autistic like behaviors induced by maternal separation stress in mice |
| url | https://doi.org/10.1371/journal.pone.0292631 |
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