Subchronic Alpha-Linolenic Acid Treatment Enhances Brain Plasticity and Exerts an Antidepressant Effect: A Versatile Potential Therapy for Stroke
Subchronic Alpha-Linolenic Acid Treatment Enhances Brain Plasticity and Exerts an Antidepressant Effect: A Versatile Potential Therapy for Stroke
复制标题
DOI：
10.1038/npp.2009.84
复制
发表时间：
2009-11-01
影响因子：
7.6
通讯作者：
Heurteaux, Catherine
中科院分区：
文献类型：
--
作者：
Blondeau, Nicolas;Nguemeni, Carine;Heurteaux, Catherine
已知Omega-3多不饱和脂肪酸在几种神经和精神疾病中具有治疗潜力。然而，这些影响的分子作用机制还没有得到很好的阐明。我们以前表明，α-亚麻酸（ALA）减少缺血性脑损伤后，单次治疗。为了跟进这一发现，我们研究了亚慢性ALA治疗是否促进神经元可塑性。连续三次注射神经保护剂量的ALA增加了神经发生和参与突触功能的关键蛋白质的表达，即突触素-1，VAMP-2和SNAP-25，以及支持谷氨酸能神经传递的蛋白质，即V-GLUT 1和V-GLUT 2。这些影响与脑源性神经营养因子（BDNF）蛋白水平的增加相关，无论是在体外使用神经干细胞和海马培养物，还是在体内，亚慢性ALA治疗后。鉴于BDNF具有抗抑郁活性，这促使我们测试亚慢性ALA治疗是否可以产生抗抑郁样行为。ALA治疗的小鼠与溶媒治疗的动物相比，抑郁样行为的测量值显著降低，这表明ALA治疗的另一个方面可以通过潜在地将急性神经保护与长期修复/代偿可塑性相结合来刺激功能性卒中恢复。事实上，三次连续注射ALA增强了保护作用，无论是作为预处理，其中它在大脑中动脉闭塞1小时后24小时减少了缺血后梗死体积，还是作为治疗后治疗，其中它在缺血后10天将动物存活率提高了三倍。Neuropsychopharmacology（2009）34，2548-2559; doi：10.1038/npp.2009.84; 2009年7月29日在线发表
Omega-3 polyunsaturated fatty acids are known to have therapeutic potential in several neurological and psychiatric disorders. However, the molecular mechanisms of action underlying these effects are not well elucidated. We previously showed that alpha-linolenic acid (ALA) reduced ischemic brain damage after a single treatment. To follow-up this finding, we investigated whether subchronic ALA treatment promoted neuronal plasticity. Three sequential injections with a neuroprotective dose of ALA increased neurogenesis and expression of key proteins involved in synaptic functions, namely, synaptophysin-1, VAMP-2, and SNAP-25, as well as proteins supporting glutamatergic neurotransmission, namely, V-GLUT1 and V-GLUT2. These effects were correlated with an increase in brain-derived neurotrophic factor (BDNF) protein levels, both in vitro using neural stem cells and hippocampal cultures and in vivo, after subchronic ALA treatment. Given that BDNF has antidepressant activity, this led us to test whether subchronic ALA treatment could produce antidepressant-like behavior. ALA-treated mice had significantly reduced measures of depressive-like behavior compared with vehicle-treated animals, suggesting another aspect of ALA treatment that could stimulate functional stroke recovery by potentially combining acute neuroprotection with long-term repair/compensatory plasticity. Indeed, three sequential injections of ALA enhanced protection, either as a pretreatment, wherein it reduced post-ischemic infarct volume 24 h after a 1-hour occlusion of the middle cerebral artery or as post-treatment therapy, wherein it augmented animal survival rates by threefold 10 days after ischemia. Neuropsychopharmacology (2009) 34, 2548-2559; doi:10.1038/npp.2009.84; published online 29 July 2009