Stanojevic Jelena B, Zeljkovic Milica, Dragic Milorad, Stojanovic Ivana R, Ilic Tihomir V, Stevanovic Ivana D, Ninkovic Milica B
Institute for Biochemistry, Faculty of Medicine, University of Niš, Niš, Serbia.
Medical Faculty of Military Medical Academy, University of Defense, Belgrade, Serbia.
Front Aging Neurosci. 2023 May 18;15:1161678. doi: 10.3389/fnagi.2023.1161678. eCollection 2023.
Intracerebroventricularly (icv) injected streptozotocin (STZ) is a widely used model for sporadic Alzheimer's disease (sAD)-like pathology, marked by oxidative stress-mediated pathological progression. Intermittent theta burst stimulation (iTBS) is a noninvasive technique for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for several neurological diseases, including AD. The present study aims to investigate the effect of the iTBS protocol on the animal model of STZ-induced sAD-like pathology in the context of antioxidant, anti-inflammatory, and anti-amyloidogenic effects in the cortex, striatum, hippocampus, and cerebellum.
Male Wistar rats were divided into four experimental groups: control (icv normal saline solution), STZ (icv STZ-3 mg/kg), STZ + iTBS (STZ rats subjected to iTBS protocol), and STZ + Placebo (STZ animals subjected to placebo iTBS noise artifact). Biochemical assays and immunofluorescence microscopy were used to evaluate functional and structural changes.
The icv STZ administration induces oxidative stress and attenuates antioxidative capacity in all examined brain regions. iTBS treatment significantly reduced oxidative and nitrosative stress parameters. Also, iTBS decreased Aβ- and APP levels. The iTBS enhances antioxidative capacity reported as elevated activity of its enzymatic and non-enzymatic components. In addition, iTBS elevated BDNF expression and attenuated STZ-induced astrogliosis confirmed by decreased GFAP/VIM/C3 cell reactivity in the hippocampus.
Our results provide experimental evidence for the beneficial effects of the applied iTBS protocol in attenuating oxidative stress, increasing antioxidant capacity and decreasing reactive astrogliosis in STZ-administrated rats.
脑室内注射链脲佐菌素（STZ）是一种广泛应用的散发性阿尔茨海默病（sAD）样病理模型，其特征为氧化应激介导的病理进展。间歇性θ波爆发刺激（iTBS）是一种用于脑活动刺激的非侵入性技术，能够诱导长期增强样可塑性，是包括AD在内的几种神经疾病的一种有前景的治疗方法。本研究旨在探讨iTBS方案对STZ诱导的sAD样病理动物模型的影响，涉及皮质、纹状体、海马和小脑中的抗氧化、抗炎和抗淀粉样生成作用。
将雄性Wistar大鼠分为四个实验组：对照组（脑室内注射生理盐水）、STZ组（脑室内注射3 mg/kg STZ）、STZ + iTBS组（接受iTBS方案的STZ大鼠）和STZ + 安慰剂组（接受安慰剂iTBS噪声伪迹的STZ动物）。采用生化分析和免疫荧光显微镜评估功能和结构变化。
脑室内注射STZ可在所有检测的脑区诱导氧化应激并减弱抗氧化能力。iTBS治疗显著降低了氧化和亚硝化应激参数。此外，iTBS降低了Aβ和APP水平。iTBS增强了抗氧化能力，表现为其酶促和非酶促成分的活性升高。此外，iTBS提高了脑源性神经营养因子（BDNF）的表达，并通过海马中GFAP/VIM/C3细胞反应性降低证实减弱了STZ诱导的星形胶质细胞增生。
我们的结果为应用的iTBS方案在减轻STZ给药大鼠的氧化应激、提高抗氧化能力和减少反应性星形胶质细胞增生方面的有益作用提供了实验证据。
