Chronic Administration of Thymoquinone Enhances Adult Hippocampal Neurogenesis and Improves Memory in Rats Via Regulating the BDNF Signaling Pathway.

Autor: Al Mamun A; Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan.; Department of Neurology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, 77030, USA., Matsuzaki K; Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan., Islam R; Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan.; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06510, USA., Hossain S; Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan.; Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka, 1342, Bangladesh., Hossain ME; Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan.; Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Katakura M; Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan.; Department of Nutritional Physiology, Faculty of Pharmaceutical Sciences, Josai University, Sakado, 350-0295, Japan., Arai H; Department of Geriatrics & Gerontology Division of Brain Science Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Miyagi, Japan., Shido O; Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan., Hashimoto M; Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan. michio1@med.shimane-u.ac.jp.
Jazyk: angličtina
Zdroj: Neurochemical research [Neurochem Res] 2022 Apr; Vol. 47 (4), pp. 933-951. Date of Electronic Publication: 2021 Dec 02.
DOI: 10.1007/s11064-021-03495-8
Abstrakt: Thymoquinone is a pharmacologically active component of Nigella sativa Linn. seeds. Despite the diverse neuropharmacological attributes of TQ, limited reports related to adult neurogenesis and memory research are available. In this study, we investigated the effects of TQ on the proliferation and neural differentiation of cultured neural stem/progenitor cells (NSCs/NPCs). We also investigated the effect of TQ chronic administration on neurogenesis and memory in adult rats. Under proliferation conditions, TQ (0.05-0.3 μM) significantly increased NSCs/NPCs viability, neurosphere diameter, and cell count. TQ treatment under differentiation conditions increased the proportion of cells positive for Tuj1 (a neuronal marker). Furthermore, chronic oral administration of TQ (25 mg/kg/day for 12 weeks) to adult rats increased the number of bromodeoxyuridine (BrdU)-immunopositive cells double-stained with a mature neuronal marker, neuronal nuclei (NeuN), and a proliferation marker, doublecortin (Dcx), in the dentate gyrus of the hippocampus. TQ-administered rats showed a profound beneficial effect on avoidance-related learning ability, associated with an increase in the hippocampal mRNA and protein levels of brain-derived neurotrophic factor (BDNF), as measured by both real-time PCR and ELISA. Western blot analysis revealed that TQ stimulates the phosphorylation of cAMP-response element-binding protein (CREB), the upstream signaling molecule in the BDNF pathway. Furthermore, chronic administration of TQ decreased lipid peroxide and reactive oxygen species levels in the hippocampus. Taken together, our results suggest that TQ plays a role in memory improvement in adult rats and that the CREB/BDNF signaling pathways are involved in mediating the actions of TQ in hippocampal neurogenesis.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE