Nox4 Promotes Neural Stem/Precursor Cell Proliferation and Neurogenesis in the Hippocampus and Restores Memory Function Following Trimethyltin-Induced Injury

Yoji Yoshikawa, Tetsuro Ago, Junya Kuroda, Yoshinobu Wakisaka, Masaki Tachibana, Motohiro Komori, Tomoya Shibahara, Hideyuki Nakashima, Kinichi Nakashima, Takanari Kitazono

研究成果: ジャーナルへの寄稿記事

抄録

Reactive oxygen species (ROS) modulate the growth of neural stem/precursor cells (NS/PCs) and participate in hippocampus-associated learning and memory. However, the origin of these regulatory ROS in NS/PCs is not fully understood. In the present study, we found that Nox4, a ROS-producing NADPH oxidase family protein, is expressed in primary cultured NS/PCs and in those of the adult mouse brain. Nox inhibitors VAS 2870 and GKT137831 or Nox4 deletion attenuated bFGF-induced proliferation of cultured NS/PCs, while lentivirus-mediated Nox4 overexpression increased the production of H 2 O 2 , the phosphorylation of Akt, and the proliferation of cultured NS/PCs. Nox4 did not significantly affect the potential of cultured NS/PCs to differentiate into neurons or astrocytes. The histological and functional development of the hippocampus appeared normal in Nox4 / mice. Although pathological and functional damages in the hippocampus induced by the neurotoxin trimethyltin were not significantly different between wild-type and Nox4 / mice, the post-injury reactive proliferation of NS/PCs and neurogenesis in the subgranular zone (SGZ) of the dentate gyrus were significantly impaired in Nox4 / animals. Restoration from the trimethyltin-induced impairment in recognition and spatial working memory was also significantly attenuated in Nox4 / mice. Collectively, our findings suggest that Nox4 participates in NS/PC proliferation and neurogenesis in the hippocampus following injury, thereby helping to restore memory function.

元の言語英語
ページ(範囲)193-205
ページ数13
ジャーナルNeuroscience
398
DOI
出版物ステータス出版済み - 2 1 2019

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Neural Stem Cells
Neurogenesis
Hippocampus
Cell Proliferation
Wounds and Injuries
Reactive Oxygen Species
Lentivirus
NADPH Oxidase
Dentate Gyrus
Neurotoxins
trimethyltin
Short-Term Memory
Astrocytes
Phosphorylation
Learning
Neurons
Brain
Growth

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

これを引用

Nox4 Promotes Neural Stem/Precursor Cell Proliferation and Neurogenesis in the Hippocampus and Restores Memory Function Following Trimethyltin-Induced Injury. / Yoshikawa, Yoji; Ago, Tetsuro; Kuroda, Junya; Wakisaka, Yoshinobu; Tachibana, Masaki; Komori, Motohiro; Shibahara, Tomoya; Nakashima, Hideyuki; Nakashima, Kinichi; Kitazono, Takanari.

:: Neuroscience, 巻 398, 01.02.2019, p. 193-205.

研究成果: ジャーナルへの寄稿記事

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abstract = "Reactive oxygen species (ROS) modulate the growth of neural stem/precursor cells (NS/PCs) and participate in hippocampus-associated learning and memory. However, the origin of these regulatory ROS in NS/PCs is not fully understood. In the present study, we found that Nox4, a ROS-producing NADPH oxidase family protein, is expressed in primary cultured NS/PCs and in those of the adult mouse brain. Nox inhibitors VAS 2870 and GKT137831 or Nox4 deletion attenuated bFGF-induced proliferation of cultured NS/PCs, while lentivirus-mediated Nox4 overexpression increased the production of H 2 O 2 , the phosphorylation of Akt, and the proliferation of cultured NS/PCs. Nox4 did not significantly affect the potential of cultured NS/PCs to differentiate into neurons or astrocytes. The histological and functional development of the hippocampus appeared normal in Nox4 − / − mice. Although pathological and functional damages in the hippocampus induced by the neurotoxin trimethyltin were not significantly different between wild-type and Nox4 − / − mice, the post-injury reactive proliferation of NS/PCs and neurogenesis in the subgranular zone (SGZ) of the dentate gyrus were significantly impaired in Nox4 − / − animals. Restoration from the trimethyltin-induced impairment in recognition and spatial working memory was also significantly attenuated in Nox4 − / − mice. Collectively, our findings suggest that Nox4 participates in NS/PC proliferation and neurogenesis in the hippocampus following injury, thereby helping to restore memory function.",
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AU - Ago, Tetsuro

AU - Kuroda, Junya

AU - Wakisaka, Yoshinobu

AU - Tachibana, Masaki

AU - Komori, Motohiro

AU - Shibahara, Tomoya

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