胎生期バルプロ酸曝露と自閉スペクトラム症 -発達神経毒性メカニズムと動物モデルの統合的考察-
DOI:
https://doi.org/10.51094/jxiv.905キーワード:
自閉スペクトラム症、 バルプロ酸、 環境要因、 脳オルガノイド、 DOHaD仮説抄録
自閉スペクトラム症(ASD)の有病率は近年増加傾向にあり、最新の推定では米国で約2.7 %の子どもが診断を受けている。ASDの原因は複雑で、遺伝的要因と環境要因の相互作用によって引き起こされると考えられている。環境要因の中でも、抗てんかん薬として広く使用されているバルプロ酸(VPA)の胎生期曝露が、ASDリスクを増加させることが疫学研究で示されており、そのメカニズムの解明は重要な研究課題となっている。本総説では、VPA曝露とASDの関連について、発達神経毒性メカニズムと動物モデルを中心に統合的に考察した。VPAの発達神経毒性は多面的であり、エピジェネティックな修飾、神経幹細胞の増殖・分化、シナプス形成、神経伝達物質システムなど、広範な影響を及ぼす。これらの変化は、ASDで観察される行動異常や神経学的特徴と密接に関連していると考えられる。VPA曝露ASDモデル動物は、ヒトのASDに類似した行動異常と神経学的変化を示し、ASDの病態メカニズムの解明に重要な役割を果たしている。VPAなどの特定の環境要因がASDの原因となるケースは全体の一部であるが、これらの研究は予防可能なリスク因子の特定やASDの病態メカニズムの理解に重要な貢献をする。今後の研究課題としては、遺伝と環境の相互作用のメカニズム解明、エピジェネティクス研究の発展、環境要因の時間依存性と用量依存性の詳細な解析、動物モデルの知見のヒト研究との統合、個別化医療への応用、新規治療法の開発などが挙げられる。これらの研究を通じて、ASDの複雑な病態メカニズムがより深く理解され、効果的な予防法や治療法の開発につながることが期待される。
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公開日時: 2024-09-19 00:48:43 UTC
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久保, 明澄
神谷, 沙羅
樋口, 浩輝
中村, 賢佑
左中, 彩恵
佐々木, 哲也
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