Bagheri-Mohammadi Saeid, Askari Sahar, Alani Behrang, Moosavi Maryam, Ghasemi Rasoul
Department of Physiology and Neurophysiology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Mol Neurosci. 2022 Nov;72(11):2273-2291. doi: 10.1007/s12031-022-02075-x. Epub 2022 Oct 10.
Insulin signaling disruption and caspase-3 cleavage play a pathologic role in Alzheimer's disease (AD). Evidence suggested that cinnamaldehyde (Cin), the major component of cinnamon, has the ability to act as a neuroprotective agent. However, little evidence is available to demonstrate its effectiveness in regulating the insulin and caspase-3 signaling pathways and underlying molecular mechanisms. Therefore, the present study was conducted to correlate the molecular mechanisms of these signaling pathways and Cin treatment on animal behavioral performance in an intracerebroventricular (ICV)-streptozotocin (STZ, 3 mg/kg) model. The sporadic AD rat model was treated with Cin (10 and 100 mg/kg; intraperitoneal, i.p) daily for 2 weeks. Novel object recognition (NOR), Morris water maze (MWM), and elevated plus maze (EPM) tests were performed to assess recognition/spatial memory and anxiety-like behavior, respectively. Hippocampal Aβ aggregation was assessed using Congo red staining. The activity of hippocampal caspase-3 and IRS-1/Akt/GSK-3β signaling pathways were analyzed using the Western blot technique. The results revealed that Cin (100 mg/kg, effective dose) improved recognition/spatial memory deficits and anxiety-like behavior. In addition, Cin negated the effects of STZ on Aβ aggregation and caspase-3 cleavage in the hippocampus. Furthermore, the Western blot method showed that hippocampal IRS-1/AKT/GSK-3β phosphorylation was altered in ICV-STZ animal model, while Cin modulated this signaling pathway through decreasing Phospho.IRS-1/Total.IRS-1 ratio and also increasing Phospho.Akt/Total.Akt and Phospho.GSK-3β/Total.GSK-3β ratios. These findings suggest that Cin is involved in the regulation of hippocampal IRS-1/AKT/GSK-3β and caspase-3 pathways in a sporadic AD model, and modulation of these signaling pathways also influences the animal behavioral performance.
胰岛素信号通路破坏和半胱天冬酶 - 3裂解在阿尔茨海默病（AD）中起病理作用。有证据表明，肉桂中的主要成分肉桂醛（Cin）具有神经保护剂的作用。然而，几乎没有证据表明其在调节胰岛素和半胱天冬酶 - 3信号通路及潜在分子机制方面的有效性。因此，本研究旨在关联这些信号通路的分子机制以及Cin治疗对脑室内（ICV）注射链脲佐菌素（STZ，3 mg/kg）模型动物行为表现的影响。将散发性AD大鼠模型每日腹腔注射（i.p）Cin（10和100 mg/kg），持续2周。分别进行新物体识别（NOR）、莫里斯水迷宫（MWM）和高架十字迷宫（EPM）试验，以评估识别/空间记忆和焦虑样行为。使用刚果红染色评估海马Aβ聚集情况。采用蛋白质免疫印迹技术分析海马半胱天冬酶 - 3的活性以及IRS - 1/Akt/GSK - 3β信号通路。结果显示，Cin（100 mg/kg，有效剂量）改善了识别/空间记忆缺陷和焦虑样行为。此外，Cin消除了STZ对海马Aβ聚集和半胱天冬酶 - 3裂解的影响。此外，蛋白质免疫印迹法表明，ICV - STZ动物模型中海马IRS - 1/AKT/GSK - 3β磷酸化发生改变，而Cin通过降低磷酸化IRS - 1/总IRS - 1比值以及增加磷酸化Akt/总Akt和磷酸化GSK - 3β/总GSK - 3β比值来调节该信号通路。这些发现表明，Cin参与散发性AD模型中海马IRS - 1/AKT/GSK - 3β和半胱天冬酶 - 3通路的调节，并且这些信号通路的调节也会影响动物的行为表现。
