Department of Dental Anesthesiology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka 565-871, Japan.
Department of Dental Anesthesiology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka 565-871, Japan.
Physiol Behav. 2024 Oct 15;285:114652. doi: 10.1016/j.physbeh.2024.114652. Epub 2024 Aug 7.
Patients with Alzheimer's disease (AD) present with a variety of symptoms, including core symptoms as well as behavioral and psychological symptoms. Somatosensory neural systems are generally believed to be relatively unaffected by AD until late in the course of the disease; however, somatosensory perception in patients with AD is not yet well understood. One factor that may complicate the assessment of somatosensory perception in humans centers on individual variations in pathological and psychological backgrounds. It is therefore necessary to evaluate somatosensory perception using animal models with uniform status. In the current study, we focused on the hippocampus, the primary site of AD. We first constructed a rat model of AD model using bilateral hippocampal injections of amyloid-β peptide 1-40 and ibotenic acid; sham rats received saline injections. The Morris water maze test was used to evaluate memory impairment, and the formalin test (1 % or 4 % formalin) and upper lip von Frey test were performed to compare pain perception between AD model and sham rats. Finally, histological and immunohistochemical methods were used to evaluate tissue damage and neuronal activity, respectively, in the hippocampus. AD model rats showed bilateral hippocampal damage and had memory impairment in the Morris water maze test. Furthermore, AD model rats exhibited significantly less pain-related behavior in phase 2 (the last 50 min of the 60-minute observation) of the 4 % formalin test compared with the sham rats. However, no significant changes were observed in the von Frey test. Immunohistochemical observations of the trigeminal spinal subnucleus caudalis after 4 % formalin injection revealed significantly fewer c-Fos-immunoreactive cells in AD model rats than in sham rats, reflecting reduced neuronal activity. These results indicate that AD model rats with hippocampal damage have reduced responsiveness to persistent inflammatory chemical stimuli to the orofacial region.
阿尔茨海默病（AD）患者表现出多种症状，包括核心症状以及行为和心理症状。一般认为，躯体感觉神经系统在 AD 病程的晚期之前相对不受影响；然而，AD 患者的躯体感觉感知尚不清楚。可能使人类躯体感觉感知评估复杂化的一个因素是病理和心理背景的个体差异。因此，有必要使用具有统一状态的动物模型来评估躯体感觉感知。在本研究中，我们专注于 AD 的主要部位——海马体。我们首先使用β淀粉样肽 1-40 和海人酸双侧海马注射构建 AD 模型大鼠；假手术大鼠接受生理盐水注射。使用 Morris 水迷宫测试评估记忆障碍，使用福尔马林测试（1%或 4%福尔马林）和上唇 von Frey 测试比较 AD 模型大鼠和假手术大鼠之间的疼痛感知。最后，使用组织学和免疫组织化学方法分别评估海马体中的组织损伤和神经元活性。AD 模型大鼠表现出双侧海马损伤，并且在 Morris 水迷宫测试中表现出记忆障碍。此外，与假手术大鼠相比，AD 模型大鼠在 4%福尔马林测试的第 2 阶段（观察的最后 50 分钟）中表现出明显较少的与疼痛相关的行为。然而，von Frey 测试未观察到明显变化。4%福尔马林注射后三叉神经脊束尾核的免疫组织化学观察显示，AD 模型大鼠中的 c-Fos 免疫反应性细胞明显少于假手术大鼠，反映出神经元活性降低。这些结果表明，具有海马损伤的 AD 模型大鼠对口腔区域的持续性炎症化学刺激的反应性降低。
