Increased Oxidative Stress in the Prefrontal Cortex as a Shared Feature of Depressive- and PTSD-Like Syndromes: Effects of a Standardized Herbal Antioxidant

Autor: de Munter, Johannes, Pavlov, Dmitrii, Gorlova, Anna, Sicker, Michael, Proshin, Andrey, Kalueff, Allan V., Svistunov, Andrey, Kiselev, Daniel, Nedorubov, Andrey, Morozov, Sergey, Umriukhin, Aleksei, Lesch, Klaus-Peter, Strekalova, Tatyana, Schroeter, Careen A.
Přispěvatelé: RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Front. Nutr.
Frontiers in Nutrition
Frontiers in nutrition, 8:661455. Frontiers Media S.A.
ISSN: 2296-861X
Popis: Major depression (MD) and posttraumatic stress disorder (PTSD) share common brain mechanisms and treatment strategies. Nowadays, the dramatically developing COVID-19 situation unavoidably results in stress, psychological trauma, and high incidence of MD and PTSD. Hence, the importance of the development of new treatments for these disorders cannot be overstated. Herbal medicine appears to be an effective and safe treatment with fewer side effects than classic pharmaca and that is affordable in low-income countries. Currently, oxidative stress and neuroinflammation attract increasing attention as important mechanisms of MD and PTSD. We investigated the effects of a standardized herbal cocktail (SHC), an extract of clove, bell pepper, basil, pomegranate, nettle, and other plants, that was designed as an antioxidant treatment in mouse models of MD and PTSD. In the MD model of “emotional” ultrasound stress (US), mice were subjected to ultrasound frequencies of 16–20 kHz, mimicking rodent sounds of anxiety/despair and “neutral” frequencies of 25–45 kHz, for three weeks and concomitantly treated with SHC. US-exposed mice showed elevated concentrations of oxidative stress markers malondialdehyde and protein carbonyl, increased gene and protein expression of pro-inflammatory cytokines interleukin (IL)-1β and IL-6 and other molecular changes in the prefrontal cortex as well as weight loss, helplessness, anxiety-like behavior, and neophobia that were ameliorated by the SHC treatment. In the PTSD model of the modified forced swim test (modFST), in which a 2-day swim is followed by an additional swim on day 5, mice were pretreated with SHC for 16 days. Increases in the floating behavior and oxidative stress markers malondialdehyde and protein carbonyl in the prefrontal cortex of modFST-mice were prevented by the administration of SHC. Chromatography mass spectrometry revealed bioactive constituents of SHC, including D-ribofuranose, beta-D-lactose, malic, glyceric, and citric acids that can modulate oxidative stress, immunity, and gut and microbiome functions and, thus, are likely to be active antistress elements underlying the beneficial effects of SHC. Significant correlations of malondialdehyde concentration in the prefrontal cortex with altered measures of behavioral despair and anxiety-like behavior suggest that the accumulation of oxidative stress markers are a common biological feature of MD and PTSD that can be equally effectively targeted therapeutically with antioxidant therapy, such as the SHC investigated here. © Copyright © 2021 de Munter, Pavlov, Gorlova, Sicker, Proshin, Kalueff, Svistunov, Kiselev, Nedorubov, Morozov, Umriukhin, Lesch, Strekalova and Schroeter. We thank Maria Shoshorina, Laboratory of Psychiatric Neurobiology, Sechenov University for providing excellent technical assistance for providing herbal cocktail and solvent, Neuroplast BV, The Netherlands, for technical and material support, Rene Vendeville, Voorhout, The Netherlands and Vsevolod G. Pinelis for valuable conceptual and methodological input and discussions. This publication was supported by the Open Access Publication Fund of the University of Wuerzburg. Funding. This study was supported by the Horizon 2020 Research and Innovation Program under Grant No. 728018 (Eat2beNICE) to K-PL and TS and Grant No. 101007642 (PhytoAPP, H2020-MSCA-RISE-2020) to TS and JM.
Databáze: OpenAIRE