Intravenous ascorbate improves spatial memory in middle-aged APP/PSEN1 and wild type mice.
Intravenous ascorbate improves spatial memory in middle-aged APP/PSEN1 and wild type mice.
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DOI：
10.1016/j.bbr.2014.01.044
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发表时间：
2014-05-01
影响因子：
2.7
通讯作者：
Harrison, Fiona E.
中科院分区：
文献类型：
--
作者：
Kennard, John A.;Harrison, Fiona E.
本研究调查了单次静脉内（i. v.）剂量的维生素C（抗坏血酸盐，ASC）对APP/PSEN 1小鼠（阿尔茨海默病模型）的空间记忆的影响。首先，我们证实了ASC耗尽的gulo（−/−）小鼠的摄取时间过程，这些小鼠不能合成ASC。基于ASC转运蛋白分布观察到差异组织摄取。肝脏（SVCT 1和SVCT 2）ASC在治疗后30、60和120分钟升高（125 mg/kg，静脉内），而脾脏（SVCT 2）ASC在60和120分钟增加。在2小时间隔内，皮质（脉络丛和神经元处的SVCT 2）ASC没有可检测到的变化，尽管皮质优先保留ASC。将三个年龄（3、9或20个月）的APP/PSEN 1和野生型（WT）小鼠用ASC（125 mg/kg，i. v.）或生理盐水45分钟，然后在改进的Y-迷宫上测试，这是一种空间记忆的两次试验任务。记忆力随着年龄的增长而下降，ASC治疗改善了9个月大的APP/PSEN 1和WT小鼠的表现。APP/PSEN 1小鼠相对于WT对照没有表现出行为障碍。虽然多巴胺和代谢产物DOPAC随着年龄的增长而减少，并且在盐水处理的小鼠中空间记忆的改善与多巴胺的增加相关，但急性ASC处理并没有改变丘脑核中的单胺水平。这些数据表明，改良Y-迷宫对APP/PSEN 1小鼠中与年龄相关的缺陷敏感，但对淀粉样蛋白病理所致的额外记忆缺陷不敏感。他们还表明，短期空间记忆的改善不是由于AD或单胺信号的神经病理学特征的变化。
The present study investigated the effects of a single intravenous (i.v.) dose of Vitamin C (ascorbate, ASC) on spatial memory in APP/PSEN1 mice, an Alzheimer's disease model. First, we confirmed the uptake time course in ASC-depleted gulo (−/−) mice, which cannot synthesize ASC. Differential tissue uptake was seen based on ASC transporter distribution. Liver (SVCT1 & SVCT2) ASC was elevated at 30, 60 and 120 min post-treatment (125 mg/kg, i.v.), whereas spleen (SVCT2) ASC increased at 60 and 120 min. There was no detectable change in cortical (SVCT2 at choroid plexus, and neurons) ASC within the 2-hour interval, although the cortex preferentially retained ASC. APP/PSEN1 and wild type (WT) mice at three ages (3, 9, or 20 months) were treated with ASC (125 mg/kg, i.v.) or saline 45 min before testing on the Modified Y-maze, a two-trial task of spatial memory. Memory declined with age and ASC treatment improved performance in 9 month-old APP/PSEN1 and WT mice. APP/PSEN1 mice displayed no behavioral impairment relative to WT controls. Although dopamine and metabolite DOPAC decreased in the nucleus accumbens with age, and improved spatial memory was correlated with increased dopamine in saline treated mice, acute ASC treatment did not alter monoamine levels in the nucleus accumbens. These data show that the Modified Y-maze is sensitive to age-related deficits, but not additional memory deficits due to amyloid pathology in APP/PSEN1 mice. They also suggest improvements in short-term spatial memory were not due to changes in the neuropathological features of AD or monoamine signaling.
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影响因子：
1.9
作者：
GALLAGHER, M;BURWELL, RD;BURCHINAL, M
通讯作者：
BURCHINAL, M
影响因子：
5.7
作者：
Bekker, A;Shah, R;Blanck, T
通讯作者：
Blanck, T
影响因子：
2.7
作者：
AMMASSARITEULE, M;CAPRIOLI, A
通讯作者：
CAPRIOLI, A
影响因子：
4.2
作者：
Bernardo, Alexandra;Harrison, Fiona E.;McDonald, Michael P.
通讯作者：
McDonald, Michael P.
影响因子：
2.9
作者：
DELLU, F;MAYO, W;SIMON, H
通讯作者：
SIMON, H