Laboratory of Molecular Psychiatry, INCT for Translational Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Schizophr Res. 2012 Nov;141(2-3):162-7. doi: 10.1016/j.schres.2012.08.002. Epub 2012 Sep 4.
Omega-3 has shown efficacy to prevent schizophrenia conversion in ultra-high risk population. We evaluated the efficacy of omega-3 in preventing ketamine-induced effects in an animal model of schizophrenia and its effect on brain-derived neurotrophic factor (BDNF). Omega-3 or vehicle was administered in Wistar male rats, both groups at the 30th day of life for 15days. Each group was split in two to receive along the following 7days ketamine or saline. Locomotor and exploratory activities, memory test and social interaction between pairs were evaluated at the 52nd day of life. Prefrontal-cortex, hippocampus and striatum tissues were extracted right after behavioral tasks for mRNA BDNF expression analysis. Bloods for serum BDNF were withdrawn 24h after the end of behavioral tasks. Locomotive was increased in ketamine-treated group compared to control, omega-3 and ketamine plus omega-3 groups. Ketamine group had fewer contacts and interaction compared to other groups. Working memory and short and long-term memories were significantly impaired in ketamine group compared to others. Serum BDNF levels were significantly higher in ketamine plus omega-3 group. There was no difference between groups in prefrontal-cortex, hippocampus and striatum for mRNA BDNF expression. Administration of omega-3 in adolescent rats prevents positive, negative and cognitive symptoms in a ketamine animal model of schizophrenia. Whether these findings are consequence of BDNF increase it is unclear. However, this study gives compelling evidence for larger clinical trials to confirm the use of omega-3 to prevent schizophrenia and for studies to reinforce the beneficial role of omega-3 in brain protection.
ω-3 已被证明可有效预防超高危人群的精神分裂症转化。我们评估了 ω-3 在预防精神分裂症动物模型中氯胺酮诱导作用及其对脑源性神经营养因子 (BDNF) 的影响。ω-3 或载体在 Wistar 雄性大鼠中给药，两组均在生命第 30 天开始，连续 15 天。每组再分为两组，分别在第 7 天接受氯胺酮或生理盐水。在生命第 52 天评估运动和探索活动、记忆测试和配对之间的社会互动。在行为任务后立即提取前额叶皮质、海马体和纹状体组织，用于 BDNF 表达分析。行为任务结束后 24 小时内从血液中提取血清 BDNF。与对照组、ω-3 组和氯胺酮加 ω-3 组相比，氯胺酮处理组的运动增加。与其他组相比，氯胺酮组的接触和互动较少。与其他组相比，氯胺酮组的工作记忆以及短期和长期记忆明显受损。与其他组相比，氯胺酮加 ω-3 组的血清 BDNF 水平显著升高。在前额叶皮质、海马体和纹状体中，各组之间的 BDNF 表达没有差异。在青春期大鼠中给予 ω-3 可预防氯胺酮诱导的精神分裂症动物模型中的阳性、阴性和认知症状。这些发现是否是 BDNF 增加的结果尚不清楚。然而，这项研究为更大规模的临床试验提供了有力证据，以确认 ω-3 用于预防精神分裂症，以及研究 ω-3 在大脑保护中的有益作用。
