Thymoquinone protects cultured hippocampal and human induced pluripotent stem cells-derived neurons against α-synuclein-induced synapse damage.
The seeds of Nigella sativa are used worldwide to treat various diseases and ailments. Thymoquinone (TQ) that is present in the essential oil of these seeds mediates most of the plant's diverse therapeutic effects. The present study aimed to determine whether TQ protects against α-synuclein (αSN)-induced synaptic toxicity in rat hippocampal and human induced pluripotent stem cell (hiPSC)-derived neurons. Here, we report that αSN decreased the level of synaptophysin, a protein used as an indicator of synaptic density, in cultured hippocampal and hiPSC-derived neurons. However, simultaneous treatment with αSN and TQ protected neurons against αSN-induced synapse damage, as revealed by immunostaining. Moreover, administration of TQ efficiently induced protection in these cells against αSN-induced inhibition of synaptic vesicle recycling in hippocampal and hiPSC-derived neurons as well as against mutated P123H β-synuclein (βSN) in hippocampal neurons, as revealed by experiments using the fluorescent dye FM1-43. Using a multielectrode array, we further demonstrated that the treatment of hiPSC-derived neurons with αSN induced a reduction in spontaneous firing activity, and cotreatment with αSN and TQ partially reversed this loss. These results suggest that TQ protects cultured rat primary hippocampal and hiPSC-derived neurons against αSN-induced synaptic toxicity and could be a promising therapeutic agent for patients with Parkinson's disease and dementia with Lewy bodies.
Department of Biotechnology, Graduate School of Bionics, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan.
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Alhebshi
Department of Biotechnology, Graduate School of Bionics, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan.
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Odawara
Department of Biotechnology, Graduate School of Bionics, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan.
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Gotoh
Department of Biotechnology, Graduate School of Bionics, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan. Electronic address: isuzuki@stf.teu.ac.jp.
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Suzuki
D000200:Action Potentials; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects*; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D061251:Primary Cell Culture; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity
D016227:Benzoquinones; D018696:Neuroprotective Agents; D016708:Synaptophysin; D051844:alpha-Synuclein; C003466:thymoquinone
Cultured rat hippocampal neurons; Human induced pluripotent stem cell-derived neurons; Synapse damage; Thymoquinone; α-Synuclein