Alzheimer’s disease (AD) is characterized by cognitive impairment that eventually develops into dementia. Amyloid-beta (Aβ) accumulation is a widely described hallmark in AD, and has been reported to cause olfactory dysfunction, a condition considered an early marker of the disease associated with injuries in the olfactory bulb (OB), the hippocampus (HIPP) and other odor-related cortexes. Adiponectin (APN) is an adipokine with neuroprotective effects. Studies have demonstrated that APN administration decreases Aβ neurotoxicity and Tau hyperphosphorylation in the HIPP, reducing cognitive impairment. However, there are no studies regarding the neuroprotective effects of APN in the olfactory dysfunction observed in the Aβ rat model. The aim of the present study is to determine whether the intracerebroventricular (i.c.v) administration of APN prevents the early olfactory dysfunction in an i.c.v Amyloid-beta1–42 (Aβ1–42) rat model. Hence, we evaluated olfactory function by using a battery of olfactory tests aimed to assess olfactory memory, discrimination and detection in the Aβ rat model treated with APN. In addition, we determined the number of cells expressing the neuronal nuclei (NeuN), as well as the number of microglial cells by using the ionized calcium-binding adapter molecule 1 (Iba-1) marker in the OB and, CA1, CA3, hilus and dentate gyrus (DG) in the HIPP. Finally, we determined Arginase-1 expression in both nuclei through Western blot. We observed that the i.c.v injection of Aβ decreased olfactory function, which was prevented by the i.c.v administration of APN. In accordance with the olfactory impairment observed in i.c.v Aβ-treated rats, we observed a decrease in NeuN expressing cells in the glomerular layer of the OB, which was also prevented with the i.c.v APN. Furthermore, we observed an increase of Iba-1 cells in CA1, and DG in the HIPP of the Aβ rats, which was prevented by the APN treatment. The present study describes the olfactory impairment of Aβ treated rats and evidences the protective role that APN plays in the brain, by preventing the olfactory impairment induced by Aβ1–42. These results may lead to APN-based pharmacological therapies aimed to ameliorate AD neurotoxic effects.

中文翻译：

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脑室内脂联素对β1-42淀粉样蛋白大鼠模型嗅觉障碍的保护作用

阿尔茨海默病 (AD) 的特点是认知障碍，最终发展为痴呆症。β 淀粉样蛋白 (Aβ) 积累是 AD 中广泛描述的标志，据报道会导致嗅觉功能障碍，这种情况被认为是与嗅球 (OB)、海马 (HIPP) 和嗅觉损伤相关的疾病的早期标志。其他与气味相关的皮层。脂联素（APN）是一种具有神经保护作用的脂肪因子。研究表明，APN 给药可降低 Aβ 神经毒性和 HIPP 中 Tau 过度磷酸化，从而减轻认知障碍。然而，尚无关于 APN 对 Aβ 大鼠模型中观察到的嗅觉功能障碍的神经保护作用的研究。本研究的目的是确定脑室内 (icv) 施用 APN 是否可以预防 icv 淀粉样蛋白-β1-42 (Aβ1-42) 大鼠模型中的早期嗅觉功能障碍。因此，我们通过一系列嗅觉测试来评估嗅觉功能，旨在评估接受 APN 治疗的 Aβ 大鼠模型的嗅觉记忆、辨别和检测能力。此外，我们通过在 OB 和 CA1、CA3、 HIPP 中的门和齿状回 (DG)。最后，我们通过蛋白质印迹测定了两个细胞核中精氨酸酶1的表达。我们观察到，静脉注射 Aβ 会降低嗅觉功能，而静脉注射 APN 可以防止这种情况。根据在 icv Aβ 治疗的大鼠中观察到的嗅觉损伤，我们观察到 OB 肾小球层中 NeuN 表达细胞的减少，这也可以通过 icv APN 来预防。此外，我们观察到 Aβ 大鼠的 HIPP 中 CA1 和 DG 中的 Iba-1 细胞增加，而 APN 治疗可以阻止这种增加。本研究描述了 Aβ 治疗大鼠的嗅觉损伤，并证明了 APN 通过预防 Aβ1-42 引起的嗅觉损伤在大脑中发挥的保护作用。这些结果可能会导致基于 APN 的药物治疗，旨在改善 AD 神经毒性作用。