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

IntroductionIntracerebroventricularly (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 activ...

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Main Authors: Jelena B. Stanojevic, Milica Zeljkovic, Milorad Dragic, Ivana R. Stojanovic, Tihomir V. Ilic, Ivana D. Stevanovic, Milica B. Ninkovic
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Aging Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnagi.2023.1161678/full
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author Jelena B. Stanojevic
Jelena B. Stanojevic
Milica Zeljkovic
Milorad Dragic
Ivana R. Stojanovic
Tihomir V. Ilic
Ivana D. Stevanovic
Ivana D. Stevanovic
Milica B. Ninkovic
Milica B. Ninkovic
author_facet Jelena B. Stanojevic
Jelena B. Stanojevic
Milica Zeljkovic
Milorad Dragic
Ivana R. Stojanovic
Tihomir V. Ilic
Ivana D. Stevanovic
Ivana D. Stevanovic
Milica B. Ninkovic
Milica B. Ninkovic
author_sort Jelena B. Stanojevic
collection DOAJ
description IntroductionIntracerebroventricularly (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.MethodsMale 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.ResultsThe 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.DiscussionOur 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.
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spelling doaj.art-e40efde3b93149818cc245f1a7083e0f2023-05-18T08:06:33ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652023-05-011510.3389/fnagi.2023.11616781161678Intermittent theta burst stimulation attenuates oxidative stress and reactive astrogliosis in the streptozotocin-induced model of Alzheimer’s disease-like pathologyJelena B. Stanojevic0Jelena B. Stanojevic1Milica Zeljkovic2Milorad Dragic3Ivana R. Stojanovic4Tihomir V. Ilic5Ivana D. Stevanovic6Ivana D. Stevanovic7Milica B. Ninkovic8Milica B. Ninkovic9Institute for Biochemistry, Faculty of Medicine, University of Niš, Niš, SerbiaMedical Faculty of Military Medical Academy, University of Defense, Belgrade, SerbiaLaboratory for Neurobiology, Department for General Physiology and Biophysics, Faculty of Biology, University of Belgrade, Belgrade, SerbiaLaboratory for Neurobiology, Department for General Physiology and Biophysics, Faculty of Biology, University of Belgrade, Belgrade, SerbiaInstitute for Biochemistry, Faculty of Medicine, University of Niš, Niš, SerbiaMedical Faculty of Military Medical Academy, University of Defense, Belgrade, SerbiaMedical Faculty of Military Medical Academy, University of Defense, Belgrade, SerbiaInstitute of Medical Research, Military Medical Academy, Belgrade, SerbiaMedical Faculty of Military Medical Academy, University of Defense, Belgrade, SerbiaInstitute of Medical Research, Military Medical Academy, Belgrade, SerbiaIntroductionIntracerebroventricularly (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.MethodsMale 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.ResultsThe 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.DiscussionOur 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.https://www.frontiersin.org/articles/10.3389/fnagi.2023.1161678/fullAlzheimer’s diseasestreptozotociniTBSoxidative stressastrocytes
spellingShingle Jelena B. Stanojevic
Jelena B. Stanojevic
Milica Zeljkovic
Milorad Dragic
Ivana R. Stojanovic
Tihomir V. Ilic
Ivana D. Stevanovic
Ivana D. Stevanovic
Milica B. Ninkovic
Milica B. Ninkovic
Intermittent theta burst stimulation attenuates oxidative stress and reactive astrogliosis in the streptozotocin-induced model of Alzheimer’s disease-like pathology
Frontiers in Aging Neuroscience
Alzheimer’s disease
streptozotocin
iTBS
oxidative stress
astrocytes
title Intermittent theta burst stimulation attenuates oxidative stress and reactive astrogliosis in the streptozotocin-induced model of Alzheimer’s disease-like pathology
title_full Intermittent theta burst stimulation attenuates oxidative stress and reactive astrogliosis in the streptozotocin-induced model of Alzheimer’s disease-like pathology
title_fullStr Intermittent theta burst stimulation attenuates oxidative stress and reactive astrogliosis in the streptozotocin-induced model of Alzheimer’s disease-like pathology
title_full_unstemmed Intermittent theta burst stimulation attenuates oxidative stress and reactive astrogliosis in the streptozotocin-induced model of Alzheimer’s disease-like pathology
title_short Intermittent theta burst stimulation attenuates oxidative stress and reactive astrogliosis in the streptozotocin-induced model of Alzheimer’s disease-like pathology
title_sort intermittent theta burst stimulation attenuates oxidative stress and reactive astrogliosis in the streptozotocin induced model of alzheimer s disease like pathology
topic Alzheimer’s disease
streptozotocin
iTBS
oxidative stress
astrocytes
url https://www.frontiersin.org/articles/10.3389/fnagi.2023.1161678/full
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