Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, UNAM, Campus Juriquilla, Querétaro, México.
PLoS One. 2013 Sep 26;8(9):e75745. doi: 10.1371/journal.pone.0075745. eCollection 2013.
Early olfactory dysfunction has been consistently reported in both Alzheimer's disease (AD) and in transgenic mice that reproduce some features of this disease. In AD transgenic mice, alteration in olfaction has been associated with increased levels of soluble amyloid beta protein (Aβ) as well as with alterations in the oscillatory network activity recorded in the olfactory bulb (OB) and in the piriform cortex. However, since AD is a multifactorial disease and transgenic mice suffer a variety of adaptive changes, it is still unknown if soluble Aβ, by itself, is responsible for OB dysfunction both at electrophysiological and behavioral levels. Thus, here we tested whether or not Aβ directly affects OB network activity in vitro in slices obtained from mice and rats and if it affects olfactory ability in these rodents. Our results show that Aβ decreases, in a concentration- and time-dependent manner, the network activity of OB slices at clinically relevant concentrations (low nM) and in a reversible manner. Moreover, we found that intrabulbar injection of Aβ decreases the olfactory ability of rodents two weeks after application, an effect that is not related to alterations in motor performance or motivation to seek food and that correlates with the presence of Aβ deposits. Our results indicate that Aβ disrupts, at clinically relevant concentrations, the network activity of the OB in vitro and can trigger a disruption in olfaction. These findings open the possibility of exploring the cellular mechanisms involved in early pathological AD as an approach to reduce or halt its progress.
早期嗅觉功能障碍在阿尔茨海默病（AD）和复制该疾病某些特征的转基因小鼠中均有报道。在 AD 转基因小鼠中，嗅觉改变与可溶性淀粉样β蛋白（Aβ）水平升高以及嗅球（OB）和梨状皮层记录的振荡网络活动改变有关。然而，由于 AD 是一种多因素疾病，并且转基因小鼠会遭受多种适应性变化，因此仍然不清楚可溶性 Aβ 是否本身会导致 OB 在电生理和行为水平上的功能障碍。因此，在这里我们测试了 Aβ 是否直接影响从小鼠和大鼠中获得的切片中的 OB 网络活动，以及它是否会影响这些啮齿动物的嗅觉能力。我们的结果表明，Aβ 以浓度和时间依赖的方式降低 OB 切片的网络活动，在临床相关浓度（低 nM）下以可逆的方式降低。此外，我们发现 Aβ 在腔内注射后两周会降低啮齿动物的嗅觉能力，这种作用与运动表现或寻找食物的动机改变无关，并且与 Aβ 沉积的存在相关。我们的结果表明，Aβ 以临床相关浓度破坏 OB 的网络活动体外，并可能引发嗅觉障碍。这些发现为探索 AD 早期病理过程中的细胞机制提供了可能性，作为减少或阻止其进展的一种方法。
