Department of Pharmacology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
Int J Mol Sci. 2023 Sep 23;24(19):14474. doi: 10.3390/ijms241914474.
As the population ages, a high prevalence of multimorbidity will affect the way physicians need to think about drug interactions. With microglia's important involvement in the pathology and progression of Alzheimer's disease (AD), understanding whether systemically administered drugs intended for other affections could impact microglia function, already impacted by the presence of beta-amyloid, is important. The aim of this study was to evaluate morphological changes of microglia, using in vivo 2-photon laser scanning microscopy, in a murine model of AD under systemic administration of sodium or calcium ion channel blockers in order to establish potential effects that these drugs might have on microglia under neuro-inflammatory conditions. A total of 30 mice (age 14-16 weeks, weight 20-25 g) were used, with 25 randomly divided into three groups. The remaining animals were male mice ( = 5) used as WT controls. After baseline behavior testing, all animals received daily intraperitoneal injections for 30 days according to the assigned group [WT ( = 5), Control ( = 5), Carbamazepine ( = 10), and Verapamil ( = 10)]. The results showed that the Verapamil treatment improved short-term memory and enhanced exploratory behavior in mice. The Carbamazepine treatment also improved short-term memory but did not elicit significant changes in anxiety-related behavior. Both Verapamil and Carbamazepine reduced the surveillance speed of microglia processes and changed microglia morphology in the cortex compared to the Control group. Due to their complex molecular machinery, microglia are potentially affected by drugs that do not target them specifically, and, as such, investigating these interactions could prove beneficial in our management of neurodegenerative pathologies.
随着人口老龄化，多种疾病的高发将影响医生思考药物相互作用的方式。由于小胶质细胞在阿尔茨海默病（AD）的病理和进展中起着重要作用，了解系统性给予用于其他疾病的药物是否会影响已经受到β淀粉样蛋白影响的小胶质细胞功能非常重要。本研究旨在使用体内双光子激光扫描显微镜评估 AD 小鼠模型中小胶质细胞的形态变化，该模型接受钠离子或钙离子通道阻滞剂的系统给药，以确定这些药物在神经炎症条件下对小胶质细胞可能产生的潜在影响。共使用了 30 只小鼠（年龄 14-16 周，体重 20-25g），其中 25 只随机分为三组。其余动物为雄性小鼠（ = 5），作为 WT 对照组。在基线行为测试后，所有动物根据分配的组接受为期 30 天的每日腹腔注射[WT（ = 5）、对照（ = 5）、卡马西平（ = 10）和维拉帕米（ = 10）]。结果表明，维拉帕米治疗改善了 小鼠的短期记忆并增强了探索行为。卡马西平治疗也改善了短期记忆，但对焦虑相关行为没有显著影响。与对照组相比，维拉帕米和卡马西平治疗均降低了小胶质细胞突起的监测速度并改变了皮质中小胶质细胞的形态。由于其复杂的分子机制，小胶质细胞可能受到不针对它们的药物的潜在影响，因此研究这些相互作用可能有助于我们管理神经退行性病变。
