Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Eur J Pharmacol. 2024 Nov 5;982:176879. doi: 10.1016/j.ejphar.2024.176879. Epub 2024 Aug 10.
Alzheimer's disease (AD), the most common cause of dementia, leads to neurodegeneration and cognitive decline. We investigated the therapeutic effects of L-carnitine on cognitive performance and anxiety-like behavior in a rat model of AD induced by unilateral intracerebroventricular injection of β-amyloid (Aβ). L-carnitine (100 mg/kg/day) was administered intraperitoneally for 28 consecutive days. Following this, the open-field test, novel object recognition test, elevated plus-maze test, Barnes maze test, and passive avoidance learning test were used to assess locomotor activity, recognition memory, anxiety-like behavior, spatial memory, and passive avoidance memory, respectively. Plasma and hippocampal oxidative stress markers, including total oxidant status (TOS) and total antioxidant capacity (TAC), were examined. In addition, histological investigations were performed in the dentate gyrus of the hippocampus using Congo red staining and hematoxylin and eosin staining. The injection of Aβ resulted in cognitive deficits and increased anxiety-like behavior. These changes were associated with an imbalance of oxidants and antioxidants in plasma and the hippocampus. Also, neuronal death and Aβ plaque accumulation were increased in the hippocampal dentate gyrus region. However, injection of L-carnitine improved recognition memory, spatial memory, and passive avoidance memory in AD rats. These findings provide evidence that L-carnitine may alleviate anxiety-like behavior and cognitive deficits induced by Aβ through modulating oxidative-antioxidant status and preventing Aβ plaque accumulation and neuronal death.
阿尔茨海默病（AD）是最常见的痴呆症病因，导致神经退行性变和认知能力下降。我们研究了左卡尼汀对β-淀粉样蛋白（Aβ）单侧侧脑室注射诱导的 AD 大鼠模型中认知表现和焦虑样行为的治疗作用。左卡尼汀（100mg/kg/天）连续腹腔内给药 28 天。之后，采用旷场试验、新物体识别试验、高架十字迷宫试验、巴恩斯迷宫试验和被动回避学习试验分别评估运动活性、识别记忆、焦虑样行为、空间记忆和被动回避记忆。检测血浆和海马氧化应激标志物，包括总氧化剂状态（TOS）和总抗氧化能力（TAC）。此外，通过刚果红染色和苏木精-伊红染色对海马齿状回进行组织学研究。Aβ 注射导致认知缺陷和焦虑样行为增加。这些变化与血浆和海马中氧化剂和抗氧化剂的失衡有关。此外，海马齿状回区域的神经元死亡和 Aβ 斑块积累增加。然而，左卡尼汀的注射改善了 AD 大鼠的识别记忆、空间记忆和被动回避记忆。这些发现表明，左卡尼汀可能通过调节氧化应激状态、预防 Aβ 斑块积累和神经元死亡，减轻 Aβ 诱导的焦虑样行为和认知缺陷。
