Comparative evolutionary studies on the expmssion of dementia-related genes in aging nonhuman animals

我们检测了β-淀粉样蛋白(Aβ)和β-淀粉样前体蛋白(APP)在犬神经细胞和非神经细胞组织中的免疫组织化学定位。Aβ仅在老龄犬大脑的老年斑(SP)中检测到。APP在神经元胞体和纤维中的表达与年龄无关。腺上皮细胞APP免疫阳性。因此，APP可能在狗的非神经元上皮组织中表达。用为人类分析准备的阵列膜过滤器研究了犬脑的基因表达。与大脑老化相关的基因在年老的狗的大脑中上调。然而，在衰老的大脑中，APP基因的表达并没有增加。使用计算机软件程序，尝试在二氧化硅中创建不同形状的SP。用分形维(FD)法对所得产物的结构进行了表征。低FD者较高FD者体积较小，密度较低。矽肺中低FD的SP可能与猫科动物体内的SP相对应，而矽肺中高FD的SP可能与其他动物的SP相对应。根据目前的研究结果，猫脑内SP的形成可能不同于其他动物，提示猫脑内存在特殊的Aβ沉积过程。APP可能在猫的脑和某些腺体组织中发挥重要作用(S)，并可能随着年龄的增长而在狗的脑中异常降解为A拍。然而，APP的表达在整个生命过程中是稳定的。这种APP的异常降解和Aβ的抑制可能是Aβ在犬脑中沉积的关键。

We examined the immunohistochemical localization of beta-amyloid (A beta) and beta-amyloid precursor protein (APP) in the neuronal and non-neuronal tissues of dogs. A beta was detected only in the senile plaque (SP) in cerebrum of aged dogs. APP was expressed in the neuronal cell body and fiber independent of the age. In addition, glandular epithelial cells were immunopositive for APP. Thus, it is suggested that APP may be expressed in the non-neuronal epithelial tissues in dogs.Gene expressions of the canine brain was investigated using array membrane filters prepared for human analysis. Brain aging-related genes were upregulated in the brain from aged dogs. However, the expression of the APP gene was not increased in the aged brains.An attempt to create SPs of various shapes in silica was performed, using computer software programs. The resultant structures were morphologically evaluated by the fractal dimension (FD) method. SPs with low FD seemed to be smaller in size and less dense than those with higher FD. The low-FD SPs in silico may correspond to feline SPs in vivo, and the high-FD SP in silico to SPs of other animal species. According to the present results, SP formation in the aged feline brain may be different from that of other animal species, indicating a special A beta deposition process in cats.APP may play an important function(s) in the brain and some glandular tissues, and may be abnormally degraded to A beat in the brain by aging in dogs. However, the expression of APP was stable during life. Such abnormal degradation of APP and the inhibition of A betalysis may be crucial for A beta deposition in the canine brain.