Corticotrophin releasing factor receptor 1 antagonists prevent chronic stress-induced behavioral changes and synapse loss in aged rats.
Corticotrophin releasing factor receptor 1 antagonists prevent chronic stress-induced behavioral changes and synapse loss in aged rats.
复制标题
DOI：
10.1016/j.psyneuen.2018.02.013
复制
发表时间：
2018-04
影响因子：
3.7
通讯作者：
Csernansky J
中科院分区：
文献类型：
--
作者：
Dong H;Keegan JM;Hong E;Gallardo C;Montalvo-Ortiz J;Wang B;Rice KC;Csernansky J
越来越多的证据表明，慢性压力可以改变大脑结构和功能，并促进神经精神疾病的发展，如抑郁症和阿尔茨海默氏病。虽然一些研究的结果表明，老年人的大脑更容易受到慢性压力，它仍然是未知的拮抗剂的一个关键的压力调节因子，促肾上腺皮质激素释放因子受体1（CRF 1），可以防止压力诱导的焦虑和记忆缺陷的动物模型。在这项研究中，我们评估了两种CRF 1拮抗剂R121919和antalarmin预防老年大鼠应激诱导的焦虑相关行为和记忆缺陷以及神经退行性变的潜在益处。从18月龄开始，我们对大鼠进行了3个月的隔离-束缚应激。动物亚组通过食物给予R121919或antalarmin 3个月，随后进行一系列行为、生化和形态学分析。我们发现，应激老年大鼠表现出体重减轻和皮质酮水平升高，以及焦虑相关的行为和记忆缺陷。此外，慢性应激诱导皮层树突棘和突触的损失。然而，R121919和antalarmin都防止了应激诱导的行为变化，包括焦虑相关行为和记忆缺陷，并防止了突触丢失，这可能是通过逆转HPA轴功能障碍实现的。这些结果表明，CRF 1拮抗剂可能有望作为一种潜在的治疗方法，用于预防老年人的应激诱导的焦虑和记忆缺陷。
Mounting evidence suggests that chronic stress can alter brain structure and function and promote the development of neuropsychiatric disorders, such as depression and Alzheimer’s disease. Although the results of several studies have indicated that aged brains are more vulnerable to chronic stress, it remains unknown whether antagonists of a key stress regulator, the corticotrophin releasing factor receptor 1 (CRF1), can prevent stress-induced anxiety and memory deficits in animal models. In this study, we evaluated the potential benefits of two CRF1 antagonists, R121919 and antalarmin, for preventing stress-induced anxiety-related behavioral and memory deficits and neurodegeneration in aged rats. We stressed rats using isolation-restraint for 3 months starting from the 18 months of age. Subsets of animals were administrated either R121919 or antalarmin through food chow for 3 months, followed by a series of behavioral, biochemical and morphological analyses. We found that stressed aged rats displayed body weight losses and increased corticosterone levels, as well as anxiety-related behaviors and memory deficits. Additionally, chronic stress induced a loss of cortical dendritic spines and synapses. However, R121919 and antalarmin both prevented stress-induced behavioral changes including anxiety-related behaviors and memory deficits and prevented synapse loss, perhaps through reversing HPA axis dysfunction. These results suggest that CRF1 antagonists may hold promise as a potential therapy for preventing stress-induced anxiety and memory deficits in aged individuals.
登录
查看更多内容
影响因子：
9.3
作者：
Barnum CJ;Pace TW;Hu F;Neigh GN;Tansey MG
通讯作者：
Tansey MG
DOI：
10.1523/jneurosci.0759-10.2010
发表时间：
2010-05-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bloss EB;Janssen WG;McEwen BS;Morrison JH
通讯作者：
Morrison JH
DOI：
10.1073/pnas.0908563106
发表时间：
2009-10-20
影响因子：
11.1
作者：
Hains, Avis Brennan;Vu, Mai Anh T.;Arnsten, Amy F. T.
通讯作者：
Arnsten, Amy F. T.
慢性应激加剧了tau病理学，神经退行性变化和认知性能，通过伴皮质激素释放因子受体受体依赖性机制在tauopathy的转基因小鼠模型中。
DOI：
10.1523/jneurosci.3836-11.2011
发表时间：
2011-10-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Carroll JC;Iba M;Bangasser DA;Valentino RJ;James MJ;Brunden KR;Lee VM;Trojanowski JQ
通讯作者：
Trojanowski JQ
影响因子：
19.9
作者：
Cacioppo, John T.;Hawkey, Louise C.
通讯作者：
Hawkey, Louise C.