Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, Porto Alegre, RS, Brazil.
Exp Gerontol. 2010 May;45(5):351-6. doi: 10.1016/j.exger.2010.02.001. Epub 2010 Feb 6.
Increased levels of iron in brain regions have been reported in neurodegenerative disorders as well as in normal brain aging. We have previously demonstrated that neonatal iron loading induces cognitive impairment in adult rats. Here, we evaluate the effects of neonatal iron treatment on cognition in aged rats. We also investigated the effects of a late subchronic rosuvastatin treatment on iron- and age-induced cognitive deficits. Rats received vehicle or 10.0mg/kg Fe(2+) orally at postnatal days 12-14. When animals reached the age of 23 months, they received daily intraperitoneal injections of saline or rosuvastatin (0.2 or 2.0mg/kg) for 21 days. Twenty-four hours after the last injection, they were submitted to novel object recognition training. Retention test sessions were performed 1.5 and 24h after training, in order to assess short-term and long-term memory, respectively. Results indicated that aged animals that received iron in the neonatal period showed more severe memory deficits than vehicle-treated ones, suggesting that iron potentiates age-associated memory impairments. Rosuvastatin improved recognition memory deficits associated with iron loading and aging, providing evidence that statins may be considered for the treatment of age-associated cognitive decline.
脑区铁含量升高与神经退行性疾病以及正常脑衰老有关。我们之前的研究表明,新生期铁负荷可导致成年大鼠认知功能障碍。在此,我们评估了新生期铁处理对老年大鼠认知的影响。我们还研究了晚期亚慢性瑞舒伐他汀治疗对铁和年龄诱导的认知缺陷的影响。新生大鼠在出生后第 12-14 天经口给予载体或 10.0mg/kg Fe(2+)。当动物达到 23 月龄时,每日给予腹腔注射生理盐水或瑞舒伐他汀(0.2 或 2.0mg/kg),共 21 天。最后一次注射后 24 小时,进行新物体识别训练。在训练后 1.5 和 24 小时进行保留测试,以分别评估短期和长期记忆。结果表明,新生期接受铁处理的老年动物比接受载体处理的动物表现出更严重的记忆缺陷,表明铁增强了与年龄相关的记忆损伤。瑞舒伐他汀改善了与铁负荷和衰老相关的识别记忆缺陷,为他汀类药物可能用于治疗与年龄相关的认知衰退提供了证据。