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Young Plasma Induces Antidepressant-Like Effects in Aged Rats Subjected to Chronic Mild Stress by Suppressing Indoleamine 2,3-Dioxygenase Enzyme and Kynurenine Pathway in the Prefrontal Cortex

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Abstract

Pathophysiology of depression in elderlies is linked to aging-associated increase in indoleamine 2,3-dioxygenase (IDO) levels and activity and kynurenine (Kyn) metabolites. Moreover, these aging-induced changes may alter the brain’s responses to stress. Growing evidence suggested that young plasma can positively affect brain dysfunctions in old age. The present study aimed to investigate whether the antidepressant effects of young plasma administration in aged rats subjected to chronic unpredictable mild stress (CUMS) and underlying mechanisms, focusing on the prefrontal cortex (PFC). Young (3 months old) and aged (22 months old) male rats were divided into five groups; young control, aged control, aged rats subjected to CUMS (A + CUMS), aged rats subjected to CUMS and treated with young plasma (A + CUMS + YP), and aged rats subjected to CUMS and treated with old plasma (A + CUMS + OP). Plasma was injected (1 ml, intravenously) three times per week for four weeks. Young plasma significantly improved CUMS-induced depressive-like behaviors, evidenced by the increased sucrose consumption ratio in the sucrose preference test and the reduced immobility time in the forced swimming test. Furthermore, young plasma markedly reduced the levels of interferon-gamma (IFN-γ), IDO, Kyn, and Kyn to tryptophan (Kyn/Trp) ratio in PFC tissue. Expression levels of the serotonin transporter and growth-associated protein (GAP)-43 were also significantly increased after chronic administration of young plasma. These findings provide evidence for the antidepressant effect of young plasma in old age; however, whether it improves depressive behaviors or faster recovery from stress-induced deficits is required to be elucidated.

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Acknowledgements

This study was supported by a Grant from the Aging Research Institute of Tabriz University of Medical Sciences. Our data were derived from the thesis of Arshad Ghaffari-Nasab for a Ph.D. degree in physiology (Thesis No. 60281).

Funding

This study was supported by a grant from the Aging Research Institute of Tabriz University of Medical Sciences [Grant Number 60281].

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Authors and Affiliations

  1. Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran

    Arshad Ghaffari-Nasab, Reza Badalzadeh, Gisou Mohaddes & Mohammad Reza Alipour

  2. Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Reza Badalzadeh

  3. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Gonja Javani

  4. Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Gonja Javani & Mohammad Reza Alipour

  5. Department of Neurosciences and Cognition, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Abbas Ebrahimi-kalan

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All procedures and protocols were performed in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institute of Health (NIH; Publication No. 85-23, revised 1985) and approved by the regional ethics committee of Tabriz University of Medical Sciences (No: IR.TBZMED.VCR.REC.1397.197).

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Ghaffari-Nasab, A., Badalzadeh, R., Mohaddes, G. et al. Young Plasma Induces Antidepressant-Like Effects in Aged Rats Subjected to Chronic Mild Stress by Suppressing Indoleamine 2,3-Dioxygenase Enzyme and Kynurenine Pathway in the Prefrontal Cortex. Neurochem Res 47, 358–371 (2022). https://doi.org/10.1007/s11064-021-03440-9

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