Intermittent Fasting Pretreatment Prevents Cognitive Impairment in a Rat Model of Chronic Cerebral Hypoperfusion
Intermittent Fasting Pretreatment Prevents Cognitive Impairment in a Rat Model of Chronic Cerebral Hypoperfusion
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间歇性禁食预处理可预防慢性脑灌注不足大鼠模型的认知障碍
DOI：
10.3945/jn.116.245613
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发表时间：
2017-07-01
影响因子：
4.2
通讯作者：
Zhang, Jun-Jian
中科院分区：
文献类型：
--
作者：
Hu, Yuan;Yang, Ying;Zhang, Jun-Jian
工作背景：目的：探讨间歇性禁食（intermittentfasting，IF）预处理对永久性2血管闭塞（permanent 2-vessel occlusion，2 VO）血管性痴呆大鼠认知功能障碍的影响及其机制。IF方案中的大鼠经历隔日饲料剥夺（FD）。术后6 wk采用Morris水迷宫（MWM）和新物体再认（NOR）实验评价动物的记忆能力。行为学测试后，测定大鼠海马中丙二醛和谷胱甘肽浓度、超氧化物歧化酶（SOD）活性、抗氧化酶基因表达、炎症蛋白浓度和小胶质细胞密度。自由双血管闭塞术（2 VO-AL）大鼠在训练期第4天的逃逸时间明显延长，在目标象限的时间百分比较低在NOR测试中，大鼠的辨别率（47%）分别低于2血管手术、隔日禁食（2 VO-FD）和自由采食假手术（Sham-AL）大鼠（P < 0.05）。这表明IF有助于预防血管性认知缺陷。2 VO-AL大鼠的丙二醛含量也较高（3.54与2.15和1.66 nmol/mg蛋白质相比）和较低的谷胱甘肽浓度（53.25与66.41和91.71 nmol/mg蛋白相比），（100.1与133.3和138.5 U/mg蛋白相比），抗氧化酶的基因表达较低，炎性蛋白的表达较高，海马小胶质细胞密度明显高于2 VO-FD和Sham-AL大鼠（P < 0.05）。这表明，IF具有抗氧化和抗炎作用。结论：IF预处理血管性痴呆大鼠模型提供了持续的神经保护。这些作用与减少氧化应激和神经炎症有关。
Background: Whether intermittent fasting (IF) pretreatment can prevent vascular cognitive dysfunction remains unknown to our knowledge.Objective: We investigated the effects and underlying mechanisms of IF pretreatment on cognitive dysfunction in a permanent 2-vessel occlusion (2VO) vascular dementia rat model.Methods: Male Wistar rats weighing 200 g were subjected to either IF or ad libitum feeding for 12 wk before 2VO surgery. Rats in the IF protocol underwent alternative-day feed deprivation (FD). Memory of the animals was assessed by using the Morris water maze (MWM) and the novel object recognition (NOR) test 6 wk after the surgery. After behavioral testing, malondialdehyde and glutathione concentrations, superoxide dismutase (SOD) activity, gene expression of antioxidative enzymes, inflammatory protein concentrations, and microglia density were determined in the hippocampus of rats.Results: 2-vessel occlusion operation ad libitum (2VO-AL) rats had significantly longer escape latencies on day 4 of the training phase and spent a lower percentage of time in the target quadrant (25% compared with 38% and 41%) in the MWM, and had lower discrimination ratios (47% compared with 65% and 67%) in the NOR test than 2-vessel operation and alternate-day feed deprivation (2VO-FD) and sham operation ad libitum (Sham-AL) rats, respectively (P < 0.05). This indicates that IF helps to prevent vascular cognitive deficits. 2VO-AL rats also had higher malondialdehyde (3.54 compared with 2.15 and 1.66 nmol/mg protein) and lower glutathione concentrations (53.25 compared with 66.41 and 91.71 nmol/mg protein), lower SOD activity (100.1 compared with 133.3 and 138.5 U/mg protein), lower gene expression of antioxidative enzymes, higher expression of inflammatory proteins, and higher microglia density in the hippocampus than 2VO-FD and Sham-AL rats, respectively (P < 0.05). This suggests that IF has antioxidative and anti-inflammatory effects.Conclusions: IF pretreatment provided sustained neuroprotection in a rat model of vascular dementia. These effects were associated with reduced oxidative stress and neuroinflammation.