Abstract
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.
Highlights
Depression is a multifactorial, high-economic burden and chronic disease that affects 20% of the world population and is considered as one of the top ten causes of mortality [1, 2]
The immobility time of the maternal separation (MS) mice which received rutin at a dose of 100 mg/kg significantly decreased in comparison with that of the MS group (P < 0:001)
The immobility time of the MS mice which received rutin (100 mg/kg) plus NMDA significantly increased in comparison with that of the MS group which received rutin alone (P > 0:05, Figure 1)
Summary
Depression is a multifactorial, high-economic burden and chronic disease that affects 20% of the world population and is considered as one of the top ten causes of mortality [1, 2]. MS is defined as the lack of care, short-term care, or repeated separation from mothers during early life. This type of stress can negatively affect the development of the brain and subsequently lead to impairment in social behavior. 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. 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. We concluded that NMDA receptors, at least in part, mediated the beneficial effect of rutin
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