Lesuis Sylvie L, van Hoek Beryl A C E, Lucassen Paul J, Krugers Harm J
Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
Neurobiol Learn Mem. 2017 Oct;144:27-35. doi: 10.1016/j.nlm.2017.05.016. Epub 2017 Jun 1.
In rodents, fragmented and low levels of maternal care have been implicated in age-related cognitive decline and the incidence and progression of Alzheimer's pathology. In contrast, enhancing early postnatal maternal care has been associated with improved cognitive function later in life. Here we examined whether early postnatal handling of mouse pups from postnatal days 2-9 enhanced maternal care and whether this affected cognition and Alzheimer pathology at 5 and 11months of age in the APPswe/PS1dE9 mouse model for Alzheimer's disease. Brief, 15min daily episodes of separating offspring from their dams from postnatal days 2-9 (early handling, EH) increased maternal care of the dam towards her pups upon reunion. At 11 (but not 5) months of age, EH APPswe/PS1dE1 mice displayed significantly reduced amyloid plaque pathology in the hippocampus. At this age, EH also prevented short-term working memory deficits while restoring impairments in contextual fear memory formation in APPswe/PS1dE9 mice. EH did not modulate amyloid pathology in the amygdala, nor did it affect auditory fear conditioning deficits in APPswe/PS1dE9 mice. We conclude that increased levels of maternal care during the early life period delays amyloid accumulation and cognitive decline in an Alzheimer's mouse model, involving the hippocampus, but not to the amygdala. These studies highlight the importance of the early postnatal period in modulating resilience to develop Alzheimer's pathology later in life.
在啮齿动物中，碎片化且水平较低的母性关怀与年龄相关的认知衰退以及阿尔茨海默病病理学的发生和进展有关。相比之下，增强产后早期的母性关怀与晚年认知功能的改善有关。在此，我们研究了在出生后第2至9天对小鼠幼崽进行早期处理是否会增强母性关怀，以及这是否会影响阿尔茨海默病APPswe/PS1dE9小鼠模型在5个月和11个月大时的认知及阿尔茨海默病病理学。从出生后第2至9天，每天短暂（15分钟）将幼崽与母鼠分开（早期处理，EH），这增加了母鼠在团聚时对幼崽的母性关怀。在11个月（而非5个月）大时，经过早期处理的APPswe/PS1dE1小鼠海马体中的淀粉样斑块病理学显著减轻。在这个年龄，早期处理还预防了短期工作记忆缺陷，同时恢复了APPswe/PS1dE9小鼠情境恐惧记忆形成中的损伤。早期处理并未调节杏仁核中的淀粉样病理学，也未影响APPswe/PS1dE9小鼠的听觉恐惧条件反射缺陷。我们得出结论，在生命早期增加母性关怀水平可延缓阿尔茨海默病小鼠模型中涉及海马体而非杏仁核的淀粉样蛋白积累和认知衰退。这些研究强调了产后早期在调节晚年患阿尔茨海默病病理学的恢复力方面的重要性。
