大脳辺縁系における情動・記憶・免疫系の相互干渉機構の解明

2004 Fiscal Year Annual Research Report

• Project/Area Number: 12210009
• Research Institution: Toyama Medical and Pharmaceutical University
• Principal Investigator: 西条 寿夫 富山医科薬科大学, 医学系研究科, 教授 (00189284)
• Co-Investigator(Kenkyū-buntansha): 白木 公康 富山医科薬科大学, 医学部, 教授 (50135745) ; 村口 篤 富山医科薬科大学, 医学部, 教授 (20174287) ; 倉知 正佳 富山医科薬科大学, 医学部, 教授 (80019603) ; 許 南浩 岡山大学, 大学院・医歯学総合研究科, 教授 (70173573) ; 大谷 修 富山医科薬科大学, 医学部, 教授 (90127548)
• Keywords: 情動 / 記憶 / 認知 / 免疫 / 大脳辺縁系 / ニューロン活動 / サイトカイン / 行動

Research Abstract

本研究では,扁桃体および海馬体を含む大脳辺縁系を中心とした情動・記憶・免疫システム間の相互干渉機構を,分子・遺伝子から細胞,個体(行動)レベルまでを含む学際的な研究チームにより総合的に解明した。
1.神経生理学的研究:液晶プロジェクターによるVR仮想空間呈示装置を用い、仮想空間移動課題遂行中のサル海馬体ニューロン活動を解析した。その結果、仮想空間内の特定領域で活動が上昇する場所識別ニューロンが記録され、1)3種類の仮想空間移動課題で活動が異なる、2)特定領域でのみ報酬獲得前あるいは獲得後に活動が増加する、3)特定の仮想空間移動課題で特定方向へ移動しているときのみ活動が増加するなどの特徴的な応答が認められた。これらのことから海馬体は、空間情報だけでなく、課題の種類、報酬予告、報酬獲得のような課題関連情報(非空間情報)も符号化していることが示唆された。
2.神経解剖学的研究:統合失調モデルラットを用い、発達過程の脳における神経栄養因子(BDNF)、ドーパミンなどの神経伝達物質の発現、γ-アミノ酪酸系およびグルタミン酸系ニューロン間のシナプス結合様式などを免疫組織化学、電子顕微鏡観察などにより解析した。
3.分子生物学的研究:1)ラットの脳梗塞モデルを用いて、ニューロカンが脳梗塞後の軸索伸長を制御している可能性を明らかにした。2)カイニン酸の腹腔内投与によるマウスの小脳性失調症を用いて、脳内のIL-1とIL-18が神経細胞の機能に拮抗的に作用することことを明らかにした。3)脳由来神経栄養因子(BDNF)をより安定して中枢神経系に挿入できる弱毒HSVベクター(βH)を開発するため、βHゲノムのterminalとinternal inverted repeat部位近傍の両方にβ-gal遺伝子が挿入されるように遺伝子組換えのためのプラスミッドを作成した。
4.神経心理学的研究:1)磁気共鳴画像(MRI)により内側側頭葉構造の体積を測定し検討した結果、統合失調症および統合失調型障害のいずれでも、左右の扁桃体と海馬の体積が健常者より有意に減少していた。これらの結果から、扁桃体および海馬の形態学的変化は、統合失調症への脆弱性に関連すると考えられた。2)思春期前後における海馬体積を検討した結果、男性健常者において思春期に海馬体積が有意に増大することが示された。この所見は、統合失調症で認められる海馬体積の減少所見が思春期における発達の障害に関連することを示唆する。

Research Products

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• [Book] Annual Review神経2004(柳澤信夫, 篠原幸人, 岩田 誠, 清水輝夫, 寺本 明編集) (2004)
  • Author(s): 堀 悦郎, 西条寿夫, 小野武年
  • Total Pages: 327-339
  • Publisher: 中外医学社,東京