Institute of Anatomy and Histology & Embryology, Neuroscience, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, People's Republic of China.
Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, People's Republic of China.
Neuropeptides. 2022 Dec;96:102268. doi: 10.1016/j.npep.2022.102268. Epub 2022 Jun 30.
According to many in the field，the prevalence of Alzheimer's disease (AD) in type II diabetes (T2DM) populations is considerably higher than that in the normal population. Human islet amyloid polypeptide (hIAPP) is considered to be a common risk factor for T2DM and AD. Preliminary observations around T2DM animal model show that the decrease of adult neural stem cells (NSCs) in the subventricular zone (SVZ) is accompanied by olfactory dysfunction. Furthermore, impaired olfactory function could serve as to an early predictor of neurodegeneration，which is associated with cognitive impairment. However, the synergistic effects between hIAPP and amyloid-beta (Aβ) in the brain and the neurodegeneration remains to be further clarified. In this study, olfactory capacity, synaptic density, status of NSC in SVZ, and status of newborn neurons in olfactory bulb (OB) were assessed 6 months after stereotactic injection of oligomer Aβ into the dens gyrus (DG) of hIAPP-/+ mice or wild-type homogenous mice. Our results set out that Aβ and amylin co-localized into OB and raised Aβ deposition in hIAPP mice compared with wild-type brood mice. In addition, 6 months after injection of Aβ in hIAPP mice, these mice showed increased olfactory dysfunction, significant loss of synapses, depletion of NSC in SVZ, and impaired cell renewal in OB. Our present study suggested that the synergistic effects between hIAPP and Aβ impairs olfactory function and was associated with decreased neurogenesis in adults with SVZ.
根据该领域的许多人，Ⅱ型糖尿病（T2DM）人群中阿尔茨海默病（AD）的患病率明显高于普通人群。人胰岛淀粉样多肽（hIAPP）被认为是 T2DM 和 AD 的共同危险因素。在 T2DM 动物模型的初步观察中，发现侧脑室下区（SVZ）中的成年神经干细胞（NSC）减少伴随着嗅觉功能障碍。此外，嗅觉功能障碍可作为神经退行性变的早期预测指标，而神经退行性变与认知障碍有关。然而，hIAPP 和淀粉样β（Aβ）在大脑中的协同作用以及神经退行性变仍需进一步阐明。在这项研究中，在 hIAPP-/+ 小鼠或野生型同窝小鼠的齿状回（DG）立体定向注射寡聚物 Aβ 6 个月后，评估了嗅觉能力、突触密度、SVZ 中的 NSC 状态以及嗅球（OB）中新神经元的状态。我们的结果表明，Aβ 和淀粉样肽在 OB 中共定位，并在 hIAPP 小鼠中增加了 Aβ 的沉积，而在野生型亲代小鼠中则没有。此外，在 hIAPP 小鼠中注射 Aβ 6 个月后，这些小鼠表现出嗅觉功能障碍增加、明显的突触丧失、SVZ 中的 NSC 耗竭以及 OB 中细胞更新受损。本研究表明，hIAPP 和 Aβ 的协同作用损害了嗅觉功能，并与 SVZ 中神经发生减少有关。
