Intermittent theta burst stimulation attenuates oxidative stress and reactive astrogliosis in the streptozotocin-induced model of Alzheimer's disease-like pathology

Jelena B Stanojevic; Milica Zeljkovic; Milorad Dragic; Ivana R Stojanovic; Tihomir V Ilic; Ivana D Stevanovic; Milica B Ninkovic

doi:10.3389/fnagi.2023.1161678

Intermittent theta burst stimulation attenuates oxidative stress and reactive astrogliosis in the streptozotocin-induced model of Alzheimer's disease-like pathology

Front Aging Neurosci. 2023 May 18:15:1161678. doi: 10.3389/fnagi.2023.1161678. eCollection 2023.

Authors

Jelena B Stanojevic^{1

2}, Milica Zeljkovic³, Milorad Dragic³, Ivana R Stojanovic¹, Tihomir V Ilic², Ivana D Stevanovic^{2

4}, Milica B Ninkovic^{2

4}

Affiliations

¹ Institute for Biochemistry, Faculty of Medicine, University of Niš, Niš, Serbia.
² Medical Faculty of Military Medical Academy, University of Defense, Belgrade, Serbia.
³ Laboratory for Neurobiology, Department for General Physiology and Biophysics, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
⁴ Institute of Medical Research, Military Medical Academy, Belgrade, Serbia.

Abstract

Introduction: 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.

Methods: 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.

Results: 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-_1-42 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.

Discussion: 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.

Keywords: Alzheimer’s disease; astrocytes; iTBS; oxidative stress; streptozotocin.