Effects of prenatal exposure to nicotine on spontaneous correlated wave activity and the brain development

• Project/Area Number: 19K06962
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: Kanto Gakuin University
• Principal Investigator: Momose-Sato Yoko 関東学院大学, 栄養学部, 教授 (70251501)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: ニコチン / 胎生期 / 脱分極波 / 神経系 / 発生 / 光学イメージング / 膜電位感受性色素 / 光学計測

Outline of Research at the Start

妊娠中の喫煙・受動喫煙は、胎児の脳に様々な悪影響を及ぼすことが知られている。申請者は、中枢神経系の機能発生に重要な役割を果たすと考えられる広範囲伝播性脱分極波を発見し、解析を行ってきた。本研究は、ニコチンへの暴露による胎児脳発達への影響という観点から、脱分極波を介した神経系の発生制御機構と、それに関連したニコチン型アセチルコリン受容体の役割について解析を行い、喫煙が及ぼす胎生期の神経系発生への影響について、新たな病態発生メカニズムを提唱することを目的とする。

Outline of Final Research Achievements

Correlated spontaneous activity propagating over a wide region of the central nervous system is expressed during a specific period of embryonic development. Our previous studies using an antagonist of nicotinic acetylcholine receptors raised the possibility that prenatal nicotine exposure associated with maternal smoking affects the development of neural circuit formation by interfering with the correlated wave. In the present study, we tested this hypothesis by examining the effects of nicotine in avian and mammalian embryos. The application of nicotine transiently increased, but subsequently inhibited electrical bursts associated with the correlated wave. Furthermore, chronic exposure to nicotine in ovo markedly reduced functional synaptic expression in the brainstem sensory nucleus, the parabrachial nucleus. The results suggested that prenatal nicotine exposure disrupts the initial formation of neural circuitry by inhibiting the correlated spontaneous activity.

Academic Significance and Societal Importance of the Research Achievements

妊娠中の喫煙は、胎児・新生児期における様々な脳機能障害や致死的疾患に関与していることが知られている。本研究の成果は、妊娠中の喫煙がおよぼす神経系への影響について、広範囲伝播脱分極波の阻害による神経回路網形成の異常という新たな病態メカニズムの概念を導入した。喫煙の影響は、本人の禁煙だけで解決できる問題ではなく、受動喫煙による障害をいかにして防ぎ、被った影響をいかにして是正するかが大きな社会問題となっている。本研究の成果は、臨床病態生理学のみならず、社会学的にも大きな影響をもたらすことが期待される。

Research Products

• [Journal Article] Functional development of olfactory nerve-related neural circuits in the embryonic chick forebrain revealed by voltage-sensitive dye imaging. (2022)
  • Author(s): Sato, K. and Momose-Sato, Y.
  • Journal Title: European Journal of Neuroscience Volume: 56 Issue: 6 Pages: 4914-4929
  • DOI: 10.1111/ejn.15788
  • Peer Reviewed / Open Access
• [Journal Article] Prenatal exposure to nicotine disrupts synaptic network formation by inhibiting spontaneous correlated wave activity. (2020)
  • Author(s): Momose-Sato, Y. and Sato, K.
  • Journal Title: IBRO Reports Volume: 9 Pages: 14-23
  • DOI: 10.1016/j.ibror.2020.06.003
  • Peer Reviewed / Open Access
• [Journal Article] Voltage-sensitive dye recording of glossopharyngeal nerve-related synaptic networks in the embryonic mouse brainstem. (2020)
  • Author(s): Momose-Sato, Y. and Sato, K.
  • Journal Title: IBRO Reports Volume: 6 Pages: 176-184
  • DOI: 10.1016/j.ibror.2019.05.004
  • Peer Reviewed / Open Access
• [Journal Article] Plasma IGF-1 levels are decreased after body weight gain with increasing food intake together with additive exercise. (2019)
  • Author(s): Yamada, T., Kurasawa, S., Matsuzaki, M., Momose-Sato, Y. and Tanaka, A.
  • Journal Title: Journal of Cachexia, Sarcopenia and Muscle Volume: 10 Issue: 6 Pages: 1428-1429
  • DOI: 10.1002/jcsm.12513
  • Open Access
• [Presentation] Optical recording of spontaneous oscillatory activity in the absence of external Ca2+ observed in the embryonic chick olfactory bulb. (2022)
  • Author(s): Sato, K. and Momose-Sato, Y.
  • Organizer: 第100回日本生理学会大会（京都）
• [Presentation] Optical analysis of spontaneous oscillatory activity in the absence of external Ca2+ observed in the embryonic chick cerebellum. (2022)
  • Author(s): Sato, K., Takahashi, N. and Momose-Sato, Y.
  • Organizer: 第99回日本生理学会大会（仙台）
• [Presentation] Effects of nicotine on spontaneous correlated wave activity in mammalian embryos. (2021)
  • Author(s): Momose-Sato, Y. and Sato, K.
  • Organizer: 第44回日本神経科学会大会（神戸）
• [Presentation] Optical detection of neuronal activity in the olfactory-limbic network of the embryonic chick forebrain. (2021)
  • Author(s): Sato, K. and Momose-Sato, Y.
  • Organizer: 第98回日本生理学会（web開催）
• [Presentation] Synaptic network formation controlled by spontaneous correlated wave activity is inhibited by prenatal exposure to nicotine. (2020)
  • Author(s): Momose-Sato, Y. and Sato, K.
  • Organizer: 第43回日本神経科学会（web開催）
• [Presentation] Functional development of the olfactory-limbic neural network in the embryonic chick brain: Optical imaging with a voltage-sensitive dye. (2020)
  • Author(s): Sato, K. and Momose-Sato, Y.
  • Organizer: 第43回日本神経科学会（web開催）
• [Presentation] Prenatal exposure to nicotine disrupts synaptic network formation by inhibiting spontaneous correlated wave activity. (2020)
  • Author(s): Momose-Sato, Y. and Sato, K.
  • Organizer: 第97回日本生理学会（紙上開催）
• [Presentation] Optical analysis of functional development of the glossopharyngeal nerve pathway in the mouse fetus brainstem. (2020)
  • Author(s): Sato, K. and Momose-Sato, Y.
  • Organizer: 第97回日本生理学会（紙上開催）
• [Presentation] Functional development of the mouse vestibular nucleus: Optical recording with a voltage-sensitive dye. (2019)
  • Author(s): Momose-Sato, Y. and Sato, K.
  • Organizer: 第42回日本神経科学学会（新潟）
• [Presentation] Optical analysis of functional development of the glossopharyngeal nerve pathway in the mouse fetus brainstem. (2019)
  • Author(s): Sato, K. and Momose-Sato, Y.
  • Organizer: 第42回日本神経科学学会（新潟）
• [Presentation] Exposure to nicotine during development disrupts synaptic network formation by inhibiting correlated spontaneous wave activity. (2019)
  • Author(s): Momose-Sato, Y. and Sato, K.
  • Organizer: Society for Neuroscience 49th Annual Meeting (Chicago, USA)
  • Int'l Joint Research
• [Presentation] Voltage-sensitive dye recording of glossopharyngeal nerve-related synaptic networks in the embryonic mouse brainstem. (2019)
  • Author(s): Sato, K. and Momose-Sato, Y.
  • Organizer: Society for Neuroscience 49th Annual Meeting (Chicago, USA)
  • Int'l Joint Research
• [Presentation] Plasma IGF-1 levels are decreased after body weight gain with increasing food intake together with additive exercise. (2019)
  • Author(s): Yamada, T., Kurasawa, S., Matsuzaki, M., Momose-Sato, Y. and Tanaka, A.
  • Organizer: 12th International Conference on Cachexia, Sarcopenia & Muscle Wasting (Berlin, Germany)
  • Int'l Joint Research