Frick K M, Burlingame L A, Arters J A, Berger-Sweeney J
Department of Biological Sciences, Wellesley College, Massachusetts, USA.
Neuroscience. 2000;95(1):293-307. doi: 10.1016/s0306-4522(99)00418-2.
Age-related changes in learning and memory are common in rodents. However, direct comparisons of the effects of aging on learning and memory in both males and females are lacking. The present study examined whether memory deteriorates with increasing age in C57BL/6NIA mice, and whether age-related changes in learning and memory are similar in both sexes. Male and female mice (five, 17 and 25 months of age) were tested in a battery of behavioral tasks including the Morris water maze (spatial and non-spatial reference memory), simple odor discrimination (olfactory reference memory), plus maze (anxiety/exploration), locomotor activity, and basic reflexes. Five-month-old mice learned the water maze and odor discrimination tasks rapidly. Relative to five-month-old mice, 25-month-old mice exhibited impaired spatial and olfactory reference memory, but intact non-spatial reference memory. The spatial reference memory of 17-month-old mice was also impaired, but less so than 25-month mice. Seventeen-month-old mice exhibited intact non-spatial (visual and olfactory) reference memory. Five and 25-month-old mice had similar levels of plus maze exploration and locomotor activity, whereas 17-month-old mice were more active than both groups and were slightly less exploratory than five-month-old mice. Although sex differences were not observed in the five- and 25-month groups, 17-month-old females exhibited more impaired spatial reference memory and increased anxiety relative to 17-month-old males. Estrous cycling in females deteriorated significantly with increased age; all 25-month-old females had ceased cycling and 80% of 17-month-old females displayed either irregular or absent estrous cycling. This study is the first to directly compare age-related mnemonic decline in male and female mice. The results suggest that: (i) aged mice exhibit significant deficits in spatial and olfactory reference memory relative to young mice, whereas middle-aged mice exhibit only a moderate spatial memory deficit and; (ii) spatial reference memory decline begins at an earlier age in females than in males, a finding that may be related to the cessation of estrous cycling.
与年龄相关的学习和记忆变化在啮齿动物中很常见。然而，目前缺乏对衰老对雄性和雌性学习和记忆影响的直接比较。本研究调查了C57BL/6NIA小鼠的记忆是否会随着年龄增长而衰退，以及学习和记忆的年龄相关变化在两性中是否相似。雄性和雌性小鼠（5、17和25月龄）接受了一系列行为任务测试，包括莫里斯水迷宫（空间和非空间参考记忆）、简单气味辨别（嗅觉参考记忆）、十字迷宫（焦虑/探索）、运动活动和基本反射。5月龄小鼠能快速学会水迷宫和气味辨别任务。相对于5月龄小鼠，25月龄小鼠表现出空间和嗅觉参考记忆受损，但非空间参考记忆完好。17月龄小鼠的空间参考记忆也受损，但程度低于25月龄小鼠。17月龄小鼠表现出完好的非空间（视觉和嗅觉）参考记忆。5月龄和25月龄小鼠在十字迷宫探索和运动活动方面水平相似，而17月龄小鼠比两组都更活跃，且探索性略低于5月龄小鼠。虽然在5月龄和25月龄组未观察到性别差异，但相对于17月龄雄性小鼠，17月龄雌性小鼠表现出更受损的空间参考记忆和更高的焦虑水平。雌性的发情周期随年龄增长显著恶化；所有25月龄雌性小鼠都已停止发情，80%的17月龄雌性小鼠表现出发情周期不规律或无发情周期。本研究首次直接比较了雄性和雌性小鼠与年龄相关的记忆衰退。结果表明：（i）老年小鼠相对于年轻小鼠在空间和嗅觉参考记忆方面存在显著缺陷，而中年小鼠仅表现出中度的空间记忆缺陷；（ii）雌性小鼠空间参考记忆衰退开始的年龄比雄性小鼠更早，这一发现可能与发情周期停止有关。
