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In Vivo 2-Photon Calcium Imaging in Layer 2/3 of Mice
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VPAC(2) 受容体は,マウスのスプラカイスマティック核における昼夜機能に不可欠である
Anthony J Harmar1, Hugh M Marston, Sanbing Shen
1Department of Neuroscience, University of Edinburgh, 1 George Square, United Kingdom. tony.harmar@ed.ac.uk
Cell
|June 28, 2002
まとめ
VPAC2受容体が欠けているマウスは,正常な昼夜リズムやクロック遺伝子発現を維持することができません. これは,神経ペプチドシグナル伝達が,昼間の機能において,上上ヒアズマ核における重要な役割を強調している.
科学分野:
- クロノバイオロジー クロノバイオロジー
- 神経科学は神経科学である.
- 分子生物学は分子生物学である.
背景:
- シルカディアンリズムは,スプラキアスマティック核 (SCN) によって調節されます.
- ニューロペプチドである pituitary adenylate cyclase-activating polypeptide (PACAP) とvasoactive intestinal peptide (VIP) は,SCNの機能に関与している.
- VPAC2受容体はPACAPとVIPの効果を媒介する.
研究 の 目的:
- 昼夜リズム調節におけるVPAC2受容体の役割を調査する.
- VPAC2受容体欠乏がSCNにおける時計遺伝子発現と光誘発反応に与える影響を決定する.
主な方法:
- VPAC2受容体遺伝子 (Vipr2(-/-) のゼロ変異を有するマウスの生成と分析.
- 昼間の休息/活動行動の評価.
- SCNにおけるコアクロック遺伝子 (mPer1,mPer2,mCry1) とクロック制御遺伝子 (アルギニンバソプレシン - AVP) の昼夜発現の測定.
- 夜間照明によるmPer1およびmPer2の急性誘導の評価.
主要な成果:
- Vipr2(-/-) のマウスは,休息/活動における昼夜リズムが乱れていることを示した.
- ミュータントマウスは,SCNにおける重要なクロック遺伝子 (mPer1,mPer2,mCry1) とAVPの正常な昼夜発現パターンを示すことができない.
- mPer1とmPer2の夜間光誘発発的発現は,Vipr2(-/-) のマウスでは廃止されています.
結論:
- VPAC2受容体は,正常な昼夜リズムとSCNのクロック遺伝子発現を維持するために不可欠です.
- VPAC2受容体によって媒介される細胞間神経ペプチダーギーシグナリングは,SCNの昼間機能において重要な役割を果たします.
- これらの発見は,PACAPとVIPシグナリングが生物学的タイミングを調節する上で重要であることを強調しています.
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