Shukitt-Hale B, Denisova N A, Strain J G, Joseph J A
USDA-ARS, Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Free Radic Biol Med. 1997;23(3):412-8. doi: 10.1016/s0891-5849(97)00094-4.
Administration of buthionine sulfoximine (BSO) selectively inhibits glutathione (GSH) biosynthesis, thereby inducing a GSH deficiency. Because GSH plays a critical role in intracellular antioxidant defense, decreased GSH levels in the brain may result in less oxidative stress (OS) protection. Thus, the pro-oxidant effects of dopamine (DA), which rapidly oxidizes to form reactive oxygen species, may increase. In this study, the behavioral consequences of reduced OS protection were examined by administering BSO (3.2 mg in 30 microl Ringer's solution, intracerebroventricularly) every other day for 12 d to male Fischer 344 rats. In addition, DA (15 microl of 500 microM) was administered every day; when given on the same day as BSO, it was either 1 h after BSO (BSO + DA group) or 1 h before BSO (DA + BSO group). Tests of psychomotor behavior--rod walking, wire suspension, and plank walking--were performed five times during the experiment. BSO + DA administration, but not DA + BSO, impaired performance by decreasing latency to fall in the rod and plank walk tests compared to a vehicle only (Ringer's) group. Therefore, depletion of GSH with BSO, followed by DA treatment, produced deficits in psychomotor behavior. These deficits are similar to those seen in aged rats, suggesting that the oxidation of DA coupled with a reduced capacity to respond to OS may be responsible for the induction of age-related motor behavioral deficits.
给予丁硫氨酸亚砜胺（BSO）可选择性抑制谷胱甘肽（GSH）的生物合成，从而导致GSH缺乏。由于GSH在细胞内抗氧化防御中起关键作用，脑内GSH水平降低可能导致氧化应激（OS）保护作用减弱。因此，多巴胺（DA）快速氧化形成活性氧的促氧化作用可能增强。在本研究中，通过每隔一天向雄性Fischer 344大鼠脑室内注射BSO（3.2mg溶于30微升林格氏液），持续12天，来检测OS保护作用减弱的行为后果。此外，每天给予DA（15微升500微摩尔/升）；当与BSO在同一天给药时，DA要么在BSO给药后1小时（BSO + DA组），要么在BSO给药前1小时（DA + BSO组）给予。在实验过程中对精神运动行为进行了五次测试——杆上行走、悬线和木板行走。与仅注射溶剂（林格氏液）的组相比，给予BSO + DA而非DA + BSO会通过缩短杆上行走和木板行走测试中的跌落潜伏期来损害行为表现。因此，先用BSO消耗GSH，然后进行DA处理，会导致精神运动行为缺陷。这些缺陷与老年大鼠中观察到的缺陷相似，表明DA的氧化以及对OS反应能力的降低可能是导致与年龄相关的运动行为缺陷的原因。
