Effects of a True Prophylactic Treatment on Hippocampal and Amygdala Synaptic Plasticity and Gene Expression in a Rodent Chronic Stress Model of Social Defeat.
Effects of a True Prophylactic Treatment on Hippocampal and Amygdala Synaptic Plasticity and Gene Expression in a Rodent Chronic Stress Model of Social Defeat.
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DOI：
10.3390/ijms241311193
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发表时间：
2023-07-07
影响因子：
5.6
通讯作者：
Edwards, Jeffrey G.
中科院分区：
文献类型：
--
作者：
Winzenried, Eric T.;Everett, Anna C.;Saito, Erin R.;Miller, Roxanne M.;Johnson, Taylor;Neal, Eliza;Boyce, Zachary;Smith, Calvin;Jensen, Chloe;Kimball, Spencer;Brantley, Adam;Melendez, Gabriel;Moffat, Devin;Davis, Erin;Aponik, Lyndsey;Crofts, Tyler;Dabney, Bryson;Edwards, Jeffrey G.
关键词：
创伤后应激障碍（PTSD）是一种复杂的应激相关障碍，由暴露于创伤应激引起，其特征在于重新体验，回避和过度觉醒的症状。虽然人们普遍认为大脑中涉及情绪调节和记忆的区域，杏仁核和海马-在PTSD中失调，该疾病的病理生理学还没有很好的定义，因此，药物干预非常有限。由于应激激素去甲肾上腺素和皮质醇（大鼠中的皮质酮）与该疾病密切相关，因此我们探索了预先和全身性地用普萘洛尔和米非司酮拮抗β-肾上腺素能和糖皮质激素受体是否足以减轻由改良的社交失败（SD）应激方案诱导的突触可塑性、基因表达和焦虑的病理变化。最初对年轻成年雄性Sprague道利大鼠进行焦虑预筛选。然后将大鼠暴露于SD和慢性光应激以诱导焦虑样症状。药物治疗的大鼠给予普萘洛尔和米非司酮注射之前，并继续在整个SD应力。使用竞争性ELISA血浆，场电生理学在CA 1的腹侧海马（VH）和基底外侧杏仁核（BLA），定量RT-PCR和行为分析，我们证明，我们的SD压力增加焦虑样行为，提高长时程增强（LTP）的VH和BLA，并改变盐皮质激素，糖皮质激素和谷氨酸受体的表达。这些措施在很大程度上恢复到控制水平与普萘洛尔和米非司酮的管理。我们的研究结果表明，SD应激增加了VH和BLA的LTP，并且普萘洛尔和米非司酮的预防性治疗可能有可能减轻这些和其他应激诱导的影响。
Post-traumatic stress disorder (PTSD) is a complex stress-related disorder induced by exposure to traumatic stress that is characterized by symptoms of re-experiencing, avoidance, and hyper-arousal. While it is widely accepted that brain regions involved in emotional regulation and memory—e.g., the amygdala and hippocampus—are dysregulated in PTSD, the pathophysiology of the disorder is not well defined and therefore, pharmacological interventions are extremely limited. Because stress hormones norepinephrine and cortisol (corticosterone in rats) are heavily implicated in the disorder, we explored whether preemptively and systemically antagonizing β-adrenergic and glucocorticoid receptors with propranolol and mifepristone are sufficient to mitigate pathological changes in synaptic plasticity, gene expression, and anxiety induced by a modified social defeat (SD) stress protocol. Young adult, male Sprague Dawley rats were initially pre-screened for anxiety. The rats were then exposed to SD and chronic light stress to induce anxiety-like symptoms. Drug-treated rats were administered propranolol and mifepristone injections prior to and continuing throughout SD stress. Using competitive ELISAs on plasma, field electrophysiology at CA1 of the ventral hippocampus (VH) and the basolateral amygdala (BLA), quantitative RT-PCR, and behavior assays, we demonstrate that our SD stress increased anxiety-like behavior, elevated long-term potentiation (LTP) in the VH and BLA, and altered the expression of mineralocorticoid, glucocorticoid, and glutamate receptors. These measures largely reverted to control levels with the administration of propranolol and mifepristone. Our findings indicate that SD stress increases LTP in the VH and BLA and that prophylactic treatment with propranolol and mifepristone may have the potential in mitigating these and other stress-induced effects.
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影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
2.7
作者：
Arrant, Andrew E.;Schramm-Sapyta, Nicole L.;Kuhn, Cynthia M.
通讯作者：
Kuhn, Cynthia M.
影响因子：
3
作者：
Norrholm SD;Jovanovic T;Smith AK;Binder E;Klengel T;Conneely K;Mercer KB;Davis JS;Kerley K;Winkler J;Gillespie CF;Bradley B;Ressler KJ
通讯作者：
Ressler KJ
影响因子：
3.7
作者：
Atsak P;Orre M;Bakker P;Cerliani L;Roozendaal B;Gazzola V;Moita M;Keysers C
通讯作者：
Keysers C
影响因子：
3.5
作者：
DIAMOND, DM;BENNETT, MC;ROSE, GM
通讯作者：
ROSE, GM