Okuma Y, Nomura Y
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Jpn J Pharmacol. 1998 Dec;78(4):399-404. doi: 10.1254/jjp.78.399.
To elucidate the fundamental mechanism of age-related deficiencies of learning and to develop effective drugs for intervention in age-related diseases such as learning dysfunctions, pertinent animal models that have characteristics closely similar to human dysfunctions should be established. SAM (senescence-accelerated mouse) has been established as a murine model of the SAM strains, groups of related inbred strains including nine strains of accelerated senescence-prone, short-lived mice (SAMP) and three strains of accelerated senescence-resistant, long-lived mice (SAMR). SAMP-strain mice show relatively strain-specific age-associated phenotypic pathologies such as shortened life span and early manifestation of senescence. Among the SAMP-strain mice, SAMP8 mice show an age-related deterioration in learning ability. Here, the neuropathological, neurochemical and pharmacological features of SAM are reported, especially for SAMP8. Moreover, the effects of several drugs on the biochemical and behavioral alterations in SAMP8 and the etiologic manifestation of accelerated senescence are also discussed.
为了阐明与年龄相关的学习缺陷的基本机制，并开发用于干预诸如学习功能障碍等与年龄相关疾病的有效药物，应建立具有与人类功能障碍密切相似特征的相关动物模型。SAM（衰老加速小鼠）已被确立为SAM品系的小鼠模型，该品系包括一组相关的近交系，其中有9个易发生加速衰老、寿命较短的品系（SAMP）和3个抗加速衰老、寿命较长的品系（SAMR）。SAMP品系小鼠表现出相对特定品系的与年龄相关的表型病理特征，如寿命缩短和衰老的早期表现。在SAMP品系小鼠中，SAMP8小鼠表现出与年龄相关的学习能力衰退。在此，报告了SAM的神经病理学、神经化学和药理学特征, 特别是SAMP8的相关特征。此外，还讨论了几种药物对SAMP8生化和行为改变以及加速衰老病因表现的影响。
