Rutin via Increase in the CA3 Diameter of the Hippocampus Exerted Antidepressant-Like Effect in Mouse Model of Maternal Separation Stress: Possible Involvement of NMDA Receptors

Background and Aim. Rutin is a flavonol with neuroprotective activity. The aim of the present study is to investigate the role of the glutamatergic system in the antidepressant-like effect of rutin in a mouse model of maternal separation (MS) stress focusing on histological changes in the CA3 area o...

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Main Authors: Maryam Anjomshoa, Shakiba Nasiri Boroujeni, Sorayya Ghasemi, Zahra Lorigooini, Ahmad Amiri, Shima Balali-dehkordi, Hossein Amini-khoei
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Behavioural Neurology
Online Access:http://dx.doi.org/10.1155/2020/4813616
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author Maryam Anjomshoa
Shakiba Nasiri Boroujeni
Sorayya Ghasemi
Zahra Lorigooini
Ahmad Amiri
Shima Balali-dehkordi
Hossein Amini-khoei
author_facet Maryam Anjomshoa
Shakiba Nasiri Boroujeni
Sorayya Ghasemi
Zahra Lorigooini
Ahmad Amiri
Shima Balali-dehkordi
Hossein Amini-khoei
author_sort Maryam Anjomshoa
collection DOAJ
description Background and Aim. Rutin is a flavonol with neuroprotective activity. The aim of the present study is to investigate the role of the glutamatergic system in the antidepressant-like effect of rutin in a mouse model of maternal separation (MS) stress focusing on histological changes in the CA3 area of the hippocampus. Methods. Mouse neonates were exposed to MS paradigm 3 hours daily from postnatal days (PND) 2 to 14. The control and MS mice were divided separately into 16 groups (n=8) (8 groups for each set) including mice that received normal saline, mice that received rutin at doses of 10, 50, and 100 mg/kg, mice that received NMDA at a dose of 150 mg/kg, mice that received ketamine (NMDA antagonist) at a dose of 0.25 mg/kg, mice that received NMDA antagonist plus a subeffective dose of rutin, and mice that received NMDA plus an effective dose of rutin. Forced swimming test (FST) was performed. Afterwards, the hippocampus was evaluated in cases of histopathological changes as well as expression of NR2A and NR2B genes. Results. Rutin significantly reduced immobility time in the FST. The expression of NR2A and NR2B subunits of NMDA receptor in MS mice was significantly higher than that in the control group. Rutin significantly decreased the expression of NR2B and NR2A subunits in the hippocampus. The CA3 diameter and percentage of dark neurons in the hippocampus of MS mice significantly decreased and increased, respectively, which partially reversed following rutin administration. Conclusion. Rutin, partially, through a neuroprotective effect on the hippocampus exerted antidepressant-like effect. We concluded that NMDA receptors, at least in part, mediated the beneficial effect of rutin.
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issn 0953-4180
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language English
publishDate 2020-01-01
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spelling doaj-art-4e68f85dc8944300a08cf5f336ca10a82025-02-03T01:04:22ZengWileyBehavioural Neurology0953-41801875-85842020-01-01202010.1155/2020/48136164813616Rutin via Increase in the CA3 Diameter of the Hippocampus Exerted Antidepressant-Like Effect in Mouse Model of Maternal Separation Stress: Possible Involvement of NMDA ReceptorsMaryam Anjomshoa0Shakiba Nasiri Boroujeni1Sorayya Ghasemi2Zahra Lorigooini3Ahmad Amiri4Shima Balali-dehkordi5Hossein Amini-khoei6Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, IranMedical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, IranMedical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, IranMedical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, IranMedical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, IranMedical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, IranMedical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, IranBackground and Aim. Rutin is a flavonol with neuroprotective activity. The aim of the present study is to investigate the role of the glutamatergic system in the antidepressant-like effect of rutin in a mouse model of maternal separation (MS) stress focusing on histological changes in the CA3 area of the hippocampus. Methods. Mouse neonates were exposed to MS paradigm 3 hours daily from postnatal days (PND) 2 to 14. The control and MS mice were divided separately into 16 groups (n=8) (8 groups for each set) including mice that received normal saline, mice that received rutin at doses of 10, 50, and 100 mg/kg, mice that received NMDA at a dose of 150 mg/kg, mice that received ketamine (NMDA antagonist) at a dose of 0.25 mg/kg, mice that received NMDA antagonist plus a subeffective dose of rutin, and mice that received NMDA plus an effective dose of rutin. Forced swimming test (FST) was performed. Afterwards, the hippocampus was evaluated in cases of histopathological changes as well as expression of NR2A and NR2B genes. Results. Rutin significantly reduced immobility time in the FST. The expression of NR2A and NR2B subunits of NMDA receptor in MS mice was significantly higher than that in the control group. Rutin significantly decreased the expression of NR2B and NR2A subunits in the hippocampus. The CA3 diameter and percentage of dark neurons in the hippocampus of MS mice significantly decreased and increased, respectively, which partially reversed following rutin administration. Conclusion. Rutin, partially, through a neuroprotective effect on the hippocampus exerted antidepressant-like effect. We concluded that NMDA receptors, at least in part, mediated the beneficial effect of rutin.http://dx.doi.org/10.1155/2020/4813616
spellingShingle Maryam Anjomshoa
Shakiba Nasiri Boroujeni
Sorayya Ghasemi
Zahra Lorigooini
Ahmad Amiri
Shima Balali-dehkordi
Hossein Amini-khoei
Rutin via Increase in the CA3 Diameter of the Hippocampus Exerted Antidepressant-Like Effect in Mouse Model of Maternal Separation Stress: Possible Involvement of NMDA Receptors
Behavioural Neurology
title Rutin via Increase in the CA3 Diameter of the Hippocampus Exerted Antidepressant-Like Effect in Mouse Model of Maternal Separation Stress: Possible Involvement of NMDA Receptors
title_full Rutin via Increase in the CA3 Diameter of the Hippocampus Exerted Antidepressant-Like Effect in Mouse Model of Maternal Separation Stress: Possible Involvement of NMDA Receptors
title_fullStr Rutin via Increase in the CA3 Diameter of the Hippocampus Exerted Antidepressant-Like Effect in Mouse Model of Maternal Separation Stress: Possible Involvement of NMDA Receptors
title_full_unstemmed Rutin via Increase in the CA3 Diameter of the Hippocampus Exerted Antidepressant-Like Effect in Mouse Model of Maternal Separation Stress: Possible Involvement of NMDA Receptors
title_short Rutin via Increase in the CA3 Diameter of the Hippocampus Exerted Antidepressant-Like Effect in Mouse Model of Maternal Separation Stress: Possible Involvement of NMDA Receptors
title_sort rutin via increase in the ca3 diameter of the hippocampus exerted antidepressant like effect in mouse model of maternal separation stress possible involvement of nmda receptors
url http://dx.doi.org/10.1155/2020/4813616
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