Neurobiology of Aging Laboratory, INRCA, Ancona, Italy.
Rejuvenation Res. 2010 Apr-Jun;13(2-3):144-7. doi: 10.1089/rej.2009.0937.
Alzheimer disease (AD) is associated with mitochondrial dysfunction. In this study, we investigated succinic dehydrogenase (SDH) activity in mitochondria of hippocampal CA1 pyramidal neurons obtained from 10-month-old 3xTg-AD mice, an animal model of AD, as well as from age-matched control mice PS1-KI. In SDH-positive mitochondria, we measured numeric density (Nv, number of mitochondria/microm(3) of cytoplasm), average organelle volume (V), volume density (Vv, volume fraction of mitochondria/microm(3) of cytoplasm), average length (Fmax), and the ratio (R) between the total area of the cytochemical precipitate due to SDH activity and the total mitochondrial area. Our results indicate that 3xTg-AD mitochondria show a significant decrease of Nv, increase in V and Fmax, as well as a trend toward a reduction of R, whereas Vv is unchanged. Our findings further support the idea that mitochondrial dysfunction is involved in AD and are in line with studies indicating that both amyloid precursor protein (APP) and amyloid-beta (Abeta) localize to mitochondria.
阿尔茨海默病(AD)与线粒体功能障碍有关。在这项研究中,我们研究了来自 AD 动物模型 3xTg-AD 小鼠和年龄匹配的 PS1-KI 对照小鼠海马 CA1 锥体神经元线粒体中的琥珀酸脱氢酶(SDH)活性。在 SDH 阳性线粒体中,我们测量了数值密度(Nv,每立方微米细胞质中的线粒体数量)、平均细胞器体积(V)、体积密度(Vv,细胞质中线粒体的体积分数)、平均长度(Fmax)以及由于 SDH 活性而导致的细胞化学沉淀的总面积与线粒体总面积之间的比例(R)。我们的结果表明,3xTg-AD 线粒体的 Nv 显著降低,V 和 Fmax 增加,并且 R 有降低的趋势,而 Vv 不变。我们的发现进一步支持了线粒体功能障碍与 AD 有关的观点,并且与表明淀粉样前体蛋白(APP)和淀粉样β(Abeta)都定位于线粒体的研究一致。