Biospectroscopic Imaging Provides Evidence of Hippocampal Zn Deficiency and Decreased Lipid Unsaturation in an Accelerated Aging Mouse Model.,ACS Chemical Neuroscience

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Biospectroscopic Imaging Provides Evidence of Hippocampal Zn Deficiency and Decreased Lipid Unsaturation in an Accelerated Aging Mouse Model.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2018-07-09 , DOI: 10.1021/acschemneuro.8b00193
Nicholas Fimognari _{1,

2} , Ashley Hollings _{1,

3} , Virginie Lam _{1,

4} , Rebecca J Tidy _{1,

3} , Cameron M Kewish ₅ , Matthew A Albrecht ₁ , Ryu Takechi _{1,

4} , John C L Mamo _{1,

4} , Mark J Hackett _{1,

3}

Affiliation

Western society is facing a health epidemic due to the increasing incidence of dementia in aging populations, and there are still few effective diagnostic methods, minimal treatment options, and no cure. Aging is the greatest risk factor for memory loss that occurs during the natural aging process, as well as being the greatest risk factor for neurodegenerative disease such as Alzheimer's disease. Greater understanding of the biochemical pathways that drive a healthy aging brain toward dementia (pathological aging or Alzheimer's disease), is required to accelerate the development of improved diagnostics and therapies. Unfortunately, many animal models of dementia model chronic amyloid precursor protein overexpression, which although highly relevant to mechanisms of amyloidosis and familial Alzheimer's disease, does not model well dementia during the natural aging process. A promising animal model reported to model mechanisms of accelerated natural aging and memory impairments, is the senescence accelerated murine prone strain 8 (SAMP8), which has been adopted by many research group to study the biochemical transitions that occur during brain aging. A limitation to traditional methods of biochemical characterization is that many important biochemical and elemental markers (lipid saturation, lactate, transition metals) cannot be imaged at meso- or microspatial resolution. Therefore, in this investigation, we report the first multimodal biospectroscopic characterization of the SAMP8 model, and have identified important biochemical and elemental alterations, and colocalizations, between 4 month old SAMP8 mice and the relevant control (SAMR1) mice. Specifically, we demonstrate direct evidence of Zn deficiency within specific subregions of the hippocampal CA3 sector, which colocalize with decreased lipid unsaturation. Our findings also revealed colocalization of decreased lipid unsaturation and increased lactate in the corpus callosum white matter, adjacent to the hippocampus. Such findings may have important implication for future research aimed at elucidating specific biochemical pathways for therapeutic intervention.

中文翻译：

生物光谱成像提供了加速衰老小鼠模型中海马锌缺乏和脂质不饱和度降低的证据。

由于老龄化人口中痴呆症的发病率不断上升，西方社会正面临着一种健康流行病，而且仍然缺乏有效的诊断方法，最少的治疗选择并且无法治愈。衰老是自然衰老过程中发生记忆力丧失的最大风险因素，也是神经退行性疾病（例如阿尔茨海默氏病）的最大风险因素。为了加速发展改进的诊断和治疗方法，需要对使健康的衰老大脑趋向痴呆（病理性衰老或阿尔茨海默氏病）的生化途径有更深入的了解。不幸的是，许多痴呆动物模型都模拟了慢性淀粉样蛋白前体蛋白的过度表达，尽管它与淀粉样变性病和家族性阿尔茨海默氏病的机制高度相关，在自然衰老过程中不能很好地模拟痴呆症。据报道，一种有前途的动物模型可以模拟自然加速衰老和记忆障碍的机制，它是衰老加速鼠易生菌株8（SAMP8），许多研究小组已采用该模型研究脑衰老过程中发生的生化转变。传统生物化学表征方法的局限性在于，许多重要的生物化学和元素标记（脂质饱和度，乳酸盐，过渡金属）无法以中空间或微空间分辨率成像。因此，在这项调查中，我们报告了SAMP8模型的首次多峰生物光谱表征，并确定了4个月大的SAMP8小鼠与相关对照（SAMR1）小鼠之间的重要生化和元素变化以及共定位。具体而言，我们证明了海马CA3区特定子区域内锌缺乏的直接证据，这与降低的脂质不饱和度共定位。我们的研究结果还表明，与海马体相邻的call体白质中脂质不饱和度降低和乳酸盐增加的共定位。这些发现可能对旨在阐明治疗干预的特定生化途径的未来研究具有重要意义。

更新日期：2018-06-14

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