Pusceddu Matteo M, Kelly Philip, Ariffin Nurbazilah, Cryan John F, Clarke Gerard, Dinan Timothy G
Department of Psychiatry, University College Cork, Cork, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
Teagasc, Moorepark, Cork, Ireland.
Psychoneuroendocrinology. 2015 Aug;58:79-90. doi: 10.1016/j.psyneuen.2015.04.015. Epub 2015 Apr 28.
Stressful life events, especially those in early life, can exert long-lasting changes in the brain, increasing vulnerability to mental illness especially in females. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a critical role in the development and function of the central nervous system (CNS). Thus, we investigated the influence of an eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) (80% EPA, 20% DHA) n-3 PUFAs mixture on stress-related behavioural and neurobiological responses. Sprague-Dawley female rats were subjected to an early-life stress, maternal separation (MS) procedure from postnatal days 2 to 12. Non-separated (NS) and MS rats were administered saline, EPA/DHA 0.4g/kg/day or EPA/DHA 1g/kg/day, respectively. In adulthood, EPA/DHA treated animals had a dose dependent reduction in anxiety in NS rats. Furthermore, cognitive performance in the novel object recognition task (NOR) was improved by EPA/DHA treatment in NS animals only. EPA/DHA 1g/kg/day decreased behavioural despair in the forced swim test. Notably, EPA/DHA high dose increased the translocation of GRs into the nucleus of NS rat hippocampus. However, the levels of mBDNF remained unchanged in all the experimental groups. The corticosterone response to an acute stress was blunted in MS rats and this was further attenuated by pre-treatment with EPA/DHA. Immune response and monoamine neurotransmission were significantly altered by early-life stress. In conclusion, our study supports the view that n-3 PUFAs are beneficial in neurodevelopmentally normal animals but have little positive benefit in animals exposed to early life stress.
压力性生活事件，尤其是早年发生的那些事件，可在大脑中产生持久变化，增加患精神疾病的易感性，女性尤其如此。ω-3多不饱和脂肪酸（n-3 PUFAs）在中枢神经系统（CNS）的发育和功能中起关键作用。因此，我们研究了二十碳五烯酸（EPA）/二十二碳六烯酸（DHA）（80% EPA，20% DHA）n-3 PUFAs混合物对与压力相关的行为和神经生物学反应的影响。将Sprague-Dawley雌性大鼠在出生后第2天至12天进行早年应激、母婴分离（MS）程序。未分离（NS）和MS大鼠分别给予生理盐水、0.4g/kg/天的EPA/DHA或1g/kg/天的EPA/DHA。成年后，EPA/DHA处理的动物在NS大鼠中焦虑呈剂量依赖性降低。此外，仅在NS动物中，EPA/DHA处理改善了新物体识别任务（NOR）中的认知表现。1g/kg/天的EPA/DHA降低了强迫游泳试验中的行为绝望。值得注意的是，EPA/DHA高剂量增加了NS大鼠海马体中糖皮质激素受体（GRs）向细胞核的转位。然而，所有实验组中脑源性神经营养因子（mBDNF）水平保持不变。MS大鼠对急性应激的皮质酮反应减弱，而EPA/DHA预处理进一步减弱了这种反应。早年应激显著改变了免疫反应和单胺神经传递。总之，我们的研究支持以下观点：n-3 PUFAs对神经发育正常的动物有益，但对暴露于早年应激的动物几乎没有积极益处。
