Department of Integrative Biology and Physiology, University of California at Los Angeles (UCLA), Los Angeles, California 90095, USA.
J Neurotrauma. 2011 Oct;28(10):2113-22. doi: 10.1089/neu.2011.1872. Epub 2011 Oct 4.
The pathology of traumatic brain injury (TBI) is characterized by the decreased capacity of neurons to metabolize energy and sustain synaptic function, likely resulting in cognitive and emotional disorders. Based on the broad nature of the pathology, we have assessed the potential of the omega-3 fatty acid docosahexaenoic acid (DHA) to counteract the effects of concussive injury on important aspects of neuronal function and cognition. Fluid percussion injury (FPI) or sham injury was performed, and rats were then maintained on a diet high in DHA (1.2% DHA) for 12 days. We found that DHA supplementation, which elevates brain DHA content, normalized levels of brain-derived neurotrophic factor (BDNF), synapsin I (Syn-1), cAMP-responsive element-binding protein (CREB), and calcium/calmodulin-dependent kinase II (CaMKII), and improved learning ability in FPI rats. It is known that BDNF facilitates synaptic transmission and learning ability by modulating Syn-I, CREB, and CaMKII signaling. The DHA diet also counteracted the FPI-reduced manganese superoxide dismutase (SOD) and Sir2 (a NAD+-dependent deacetylase). Given the involvement of SOD and Sir2 in promoting metabolic homeostasis, DHA may help the injured brain by providing resistance to oxidative stress. Furthermore, DHA normalized levels of calcium-independent phospholipase A2 (iPLA2) and syntaxin-3, which may help preserve membrane homeostasis and function after FPI. The overall results emphasize the potential of dietary DHA to counteract broad and fundamental aspects of TBI pathology that may translate into preserved cognitive capacity.
创伤性脑损伤 (TBI) 的病理学特征是神经元代谢能量和维持突触功能的能力下降，可能导致认知和情绪障碍。基于广泛的病理学性质，我们评估了 ω-3 脂肪酸二十二碳六烯酸 (DHA) 抵抗震荡性损伤对神经元功能和认知重要方面的影响的潜力。进行流体冲击损伤 (FPI) 或假损伤，然后让大鼠维持富含 DHA（1.2% DHA）的饮食 12 天。我们发现，DHA 补充剂可提高大脑 DHA 含量，使脑源性神经营养因子 (BDNF)、突触结合蛋白 I (Syn-1)、cAMP 反应元件结合蛋白 (CREB) 和钙/钙调蛋白依赖性激酶 II (CaMKII) 的水平正常化，并改善 FPI 大鼠的学习能力。众所周知，BDNF 通过调节 Syn-I、CREB 和 CaMKII 信号转导来促进突触传递和学习能力。DHA 饮食还对抗了 FPI 降低的锰超氧化物歧化酶 (SOD) 和 Sir2（一种 NAD+-依赖性脱乙酰酶）。鉴于 SOD 和 Sir2 参与促进代谢稳态，DHA 可能通过提供对氧化应激的抵抗力来帮助受伤的大脑。此外，DHA 使钙非依赖性磷脂酶 A2 (iPLA2) 和突触素-3 的水平正常化，这可能有助于在 FPI 后维持膜的稳态和功能。总体结果强调了饮食 DHA 抵抗 TBI 病理学广泛和基本方面的潜力，这可能转化为认知能力的保留。
