Nasal administration of mitochondria relieves depressive- and anxiety-like behaviors in male mice exposed to restraint stress through the suppression ROS/NLRP3/caspase-1/IL-1β signaling pathway.
Autor: | Mafikandi V; Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran., Seyedaghamiri F; Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran., Hosseinzadeh N; Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran., Shahabi P; Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran., Shafiee-Kandjani AR; Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran., Babaie S; Physical Medicine and Rehabilitation Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Maghsoumi-Norouzabad L; Research Center for Integrative Medicine in Aging, Tabriz University of Medical Sciences, Tabriz, Iran., Farajdokht F; Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran., Hosseini L; Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. leilahosseini337@gmail.com. |
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Jazyk: | angličtina |
Zdroj: | Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Sep 28. Date of Electronic Publication: 2024 Sep 28. |
DOI: | 10.1007/s00210-024-03487-9 |
Abstrakt: | Neuroinflammation and oxidative stress are known to be implicated in the pathogenesis of depression. Exogenous mitochondrial transplantation has exhibited beneficial effects for treating neurological disorders. Hence, this research aimed to evaluate the impact of nasal administration of mitochondria on neuroinflammation and oxidative stress in mouse models displaying depressive- and anxiety-like behaviors caused by restraint stress (RS). Thirty male BALB/c mice were divided into control, RS, and RS + 340 µg of mitochondrial. Mice were subjected to RS using an immobilization falcon tube (2 h/day) for 2 weeks except for the control group. We conducted two behavioral tests to evaluate anxiety-like behaviors: elevated plus maze (EPM) and open field test (OFT). Tail suspension test (TST) was implemented to assess depressive-like behavior. ATP and reactive oxygen species (ROS) levels were measured in the hippocampus. Besides, serum corticosterone (CORT) levels were evaluated using the ELISA method. The expression of NLRP3 inflammasome, caspase-1 (Cas-1), and IL-1β was tested by western blot. We found that mitotherapy increased the time spent in the center of OFT and open arms of the EPM, while it diminished immobility time in TST. Mitochondrial administration considerably attenuated ROS generation and CORT levels and restored ATP levels. Additionally, mitotherapy prevented RS-induced upregulation of IL-1β, cleaved Cas1/Pro Cas1 ratio, and NLRP3/1 in the hippocampus of mice. These findings suggested that the beneficial effects of intranasal mitochondria on depression and anxiety may be attributed to suppression of the ROS/NLRP3/IL-1β/caspase-1 signaling pathway. (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) |
Databáze: | MEDLINE |
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