TY  - JOUR
AU  - Stekić, Anđela
AU  - Zeljković, Milica
AU  - Zarić Kontić, Marina
AU  - Mihajlović, Katarina
AU  - Adžić, Marija
AU  - Stevanović, Ivana
AU  - Ninković, Milica
AU  - Grković, Ivana
AU  - Ilić, Tihomir V.
AU  - Nedeljković, Nadežda
AU  - Dragić, Milorad
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11159
AB  - Neurodegeneration implies progressive neuronal loss and neuroinflammation further contributing to pathology progression. It is a feature of many neurological disorders, most common being Alzheimer’s disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive stimulation which modulates excitability of stimulated brain areas through magnetic pulses. Numerous studies indicated beneficial effect of rTMS in several neurological diseases, including AD, however, exact mechanism are yet to be elucidated. We aimed to evaluate the effect of intermittent theta burst stimulation (iTBS), an rTMS paradigm, on behavioral, neurochemical and molecular level in trimethyltin (TMT)-induced Alzheimer’s-like disease model. TMT acts as a neurotoxic agent targeting hippocampus causing cognitive impairment and neuroinflammation, replicating behavioral and molecular aspects of AD. Male Wistar rats were divided into four experimental groups–controls, rats subjected to a single dose of TMT (8 mg/kg), TMT rats subjected to iTBS two times per day for 15 days and TMT sham group. After 3 weeks, we examined exploratory behavior and memory, histopathological and changes on molecular level. TMT-treated rats exhibited severe and cognitive deficit. iTBS-treated animals showed improved cognition. iTBS reduced TMT-induced inflammation and increased anti-inflammatory molecules. We examined PI3K/Akt/mTOR signaling pathway which is involved in regulation of apoptosis, cell growth and learning and memory. We found significant downregulation of phosphorylated forms of Akt and mTOR in TMT-intoxicated animals, which were reverted following iTBS stimulation. Application of iTBS produces beneficial effects on cognition in of rats with TMT-induced hippocampal neurodegeneration and that effect could be mediated via PI3K/Akt/mTOR signaling pathway, which could candidate this protocol as a potential therapeutic approach in neurodegenerative diseases such as AD.
T2  - Frontiers in Aging Neuroscience
T1  - Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model
VL  - 14
DO  - 10.3389/fnagi.2022.889983
ER  - 

@article{
author = "Stekić, Anđela and Zeljković, Milica and Zarić Kontić, Marina and Mihajlović, Katarina and Adžić, Marija and Stevanović, Ivana and Ninković, Milica and Grković, Ivana and Ilić, Tihomir V. and Nedeljković, Nadežda and Dragić, Milorad",
year = "2022",
abstract = "Neurodegeneration implies progressive neuronal loss and neuroinflammation further contributing to pathology progression. It is a feature of many neurological disorders, most common being Alzheimer’s disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive stimulation which modulates excitability of stimulated brain areas through magnetic pulses. Numerous studies indicated beneficial effect of rTMS in several neurological diseases, including AD, however, exact mechanism are yet to be elucidated. We aimed to evaluate the effect of intermittent theta burst stimulation (iTBS), an rTMS paradigm, on behavioral, neurochemical and molecular level in trimethyltin (TMT)-induced Alzheimer’s-like disease model. TMT acts as a neurotoxic agent targeting hippocampus causing cognitive impairment and neuroinflammation, replicating behavioral and molecular aspects of AD. Male Wistar rats were divided into four experimental groups–controls, rats subjected to a single dose of TMT (8 mg/kg), TMT rats subjected to iTBS two times per day for 15 days and TMT sham group. After 3 weeks, we examined exploratory behavior and memory, histopathological and changes on molecular level. TMT-treated rats exhibited severe and cognitive deficit. iTBS-treated animals showed improved cognition. iTBS reduced TMT-induced inflammation and increased anti-inflammatory molecules. We examined PI3K/Akt/mTOR signaling pathway which is involved in regulation of apoptosis, cell growth and learning and memory. We found significant downregulation of phosphorylated forms of Akt and mTOR in TMT-intoxicated animals, which were reverted following iTBS stimulation. Application of iTBS produces beneficial effects on cognition in of rats with TMT-induced hippocampal neurodegeneration and that effect could be mediated via PI3K/Akt/mTOR signaling pathway, which could candidate this protocol as a potential therapeutic approach in neurodegenerative diseases such as AD.",
journal = "Frontiers in Aging Neuroscience",
title = "Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model",
volume = "14",
doi = "10.3389/fnagi.2022.889983"
}

Stekić, A., Zeljković, M., Zarić Kontić, M., Mihajlović, K., Adžić, M., Stevanović, I., Ninković, M., Grković, I., Ilić, T. V., Nedeljković, N.,& Dragić, M.. (2022). Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model. in Frontiers in Aging Neuroscience, 14.
https://doi.org/10.3389/fnagi.2022.889983

Stekić A, Zeljković M, Zarić Kontić M, Mihajlović K, Adžić M, Stevanović I, Ninković M, Grković I, Ilić TV, Nedeljković N, Dragić M. Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model. in Frontiers in Aging Neuroscience. 2022;14.
doi:10.3389/fnagi.2022.889983 .

Stekić, Anđela, Zeljković, Milica, Zarić Kontić, Marina, Mihajlović, Katarina, Adžić, Marija, Stevanović, Ivana, Ninković, Milica, Grković, Ivana, Ilić, Tihomir V., Nedeljković, Nadežda, Dragić, Milorad, "Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model" in Frontiers in Aging Neuroscience, 14 (2022),
https://doi.org/10.3389/fnagi.2022.889983 . .