INSERM U862, Physiopathology of Synaptic Plasticity Group, Neurocentre Magendie, Bordeaux Cedex, France.
Nat Neurosci. 2011 Mar;14(3):345-50. doi: 10.1038/nn.2736. Epub 2011 Jan 30.
The corollaries of the obesity epidemic that plagues developed societies are malnutrition and resulting biochemical imbalances. Low levels of essential n-3 polyunsaturated fatty acids (n-3 PUFAs) have been linked to neuropsychiatric diseases, but the underlying synaptic alterations are mostly unknown. We found that lifelong n-3 PUFAs dietary insufficiency specifically ablates long-term synaptic depression mediated by endocannabinoids in the prelimbic prefrontal cortex and accumbens. In n-3-deficient mice, presynaptic cannabinoid CB(1) receptors (CB(1)Rs) normally responding to endocannabinoids were uncoupled from their effector G(i/o) proteins. Finally, the dietary-induced reduction of CB(1)R functions in mood-controlling structures was associated with impaired emotional behavior. These findings identify a plausible synaptic substrate for the behavioral alterations caused by the n-3 PUFAs deficiency that is often observed in western diets.
肥胖症在发达社会流行的必然结果是营养不良和由此导致的生化失衡。必需的 n-3 多不饱和脂肪酸（n-3 PUFAs）水平低与神经精神疾病有关，但潜在的突触变化大多尚不清楚。我们发现，终生 n-3 PUFAs 饮食不足会特异性消除内侧前额叶皮层和伏隔核中内源性大麻素介导的长时程突触抑制。在 n-3 缺乏的小鼠中，正常响应内源性大麻素的突触前大麻素 CB(1) 受体（CB(1)Rs）与它们的效应 G(i/o) 蛋白脱偶联。最后，饮食引起的情绪控制结构中 CB(1)R 功能的降低与情绪行为障碍有关。这些发现为 n-3 PUFAs 缺乏症经常在西方饮食中观察到的行为改变提供了一个合理的突触基础。
