Prostacyclin Promotes Degenerative Pathology in a Model of Alzheimer's Disease.
Prostacyclin Promotes Degenerative Pathology in a Model of Alzheimer's Disease.
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DOI：
10.3389/fncel.2022.769347
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发表时间：
2022
影响因子：
5.3
通讯作者：
Eriksen JL
中科院分区：
文献类型：
--
作者：
Womack TR;Vollert CT;Ohia-Nwoko O;Schmitt M;Montazari S;Beckett TL;Mayerich D;Murphy MP;Eriksen JL
阿尔茨海默病（AD）是一种进行性神经退行性疾病，是老年人群中最常见的痴呆形式。大量数据表明，慢性神经炎症可加速神经退行性病变。在AD中，慢性神经炎症导致环加氧酶上调和前列腺素H2的产生增加，前列腺素H2是许多血管活性前列腺素的前体。虽然许多前列腺素可以调节神经退行性疾病的进展是公认的，但前列腺素（PGI2）在大脑中的作用却知之甚少。我们已经进行了研究，以评估提高前列环素生物合成对AD小鼠模型的影响。前列环素表达上调显著恶化与淀粉样蛋白-β (Aβ)疾病病理相关的多项指标。与非转基因和PGI2对照小鼠相比，过表达Aβ和PGI2的小鼠表现出学习记忆受损和焦虑样行为增加。PGI2过表达加速了Aβ在脑内积累的发展，并选择性地增加了可溶性Aβ42的产生。PGI2通过改变血管长度和分支破坏微血管；Aβ的表达加重了这些作用。我们的研究结果表明，慢性前列环素表达在加速AD表型的发展中起着新的和意想不到的作用。
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is the most common form of dementia in aged populations. A substantial amount of data demonstrates that chronic neuroinflammation can accelerate neurodegenerative pathologies. In AD, chronic neuroinflammation results in the upregulation of cyclooxygenase and increased production of prostaglandin H2, a precursor for many vasoactive prostanoids. While it is well-established that many prostaglandins can modulate the progression of neurodegenerative disorders, the role of prostacyclin (PGI2) in the brain is poorly understood. We have conducted studies to assess the effect of elevated prostacyclin biosynthesis in a mouse model of AD. Upregulated prostacyclin expression significantly worsened multiple measures associated with amyloid-β (Aβ) disease pathologies. Mice overexpressing both Aβ and PGI2 exhibited impaired learning and memory and increased anxiety-like behavior compared with non-transgenic and PGI2 control mice. PGI2 overexpression accelerated the development of Aβ accumulation in the brain and selectively increased the production of soluble Aβ42. PGI2 damaged the microvasculature through alterations in vascular length and branching; Aβ expression exacerbated these effects. Our findings demonstrate that chronic prostacyclin expression plays a novel and unexpected role that hastens the development of the AD phenotype.
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影响因子：
6.1
作者：
Coma M;Serenó L;Da Rocha-Souto B;Scotton TC;España J;Sánchez MB;Rodríguez M;Agulló J;Guardia-Laguarta C;Garcia-Alloza M;Borrelli LA;Clarimón J;Lleó A;Bacskai BJ;Saura CA;Hyman BT;Gómez-Isla T
通讯作者：
Gómez-Isla T
影响因子：
9.3
作者：
Cribbs DH;Berchtold NC;Perreau V;Coleman PD;Rogers J;Tenner AJ;Cotman CW
通讯作者：
Cotman CW
DOI：
10.18632/aging.100021
发表时间：
2009-02-11
期刊：
Aging
影响因子：
--
作者：
Choi SH;Bosetti F
通讯作者：
Bosetti F
影响因子：
6.3
作者：
He, Tongrong;Santhanam, Anantha Vijay R.;Katusic, Zvonimir S.
通讯作者：
Katusic, Zvonimir S.
影响因子：
82.9
作者：
Holcomb, L;Gordon, MN;Duff, K
通讯作者：
Duff, K