TY  - JOUR
AU  - Dragić, Milorad
AU  - Zeljković, Milica
AU  - Stevanović, Ivana
AU  - Adžić, Marija
AU  - Stekić, Anđela
AU  - Mihajlović, Katarina
AU  - Grković, Ivana
AU  - Ilić, Nela
AU  - Ilić, Tihomir V.
AU  - Nedeljković, Nadežda
AU  - Ninković, Milica
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10082
AB  - Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by autoimmune-mediated inflammation in the central nervous system. Purinergic signaling is critically involved in MS-associated neuroinflammation and its most widely applied animal model—experimental autoimmune encephalomyelitis (EAE). A promising but poorly understood approach in the treatment of MS is repetitive transcranial magnetic stimulation. In the present study, we aimed to investigate the effect of continuous theta-burst stimulation (CTBS), applied over frontal cranial bone, on the adenosine-mediated signaling system in EAE, particularly on CD73/A2AR/A1R in the context of neuroinflammatory activation of glial cells. EAE was induced in two-month-old female DA rats and in the disease peak treated with CTBS protocol for ten consecutive days. Lumbosacral spinal cord was analyzed immunohistochemically for adenosine-mediated signaling components and pro- and anti-inflammatory factors. We found downregulated IL-1β and NF- κB-ir and upregulated IL-10 pointing towards a reduction in the neuroinflammatory process in EAE animals after CTBS treatment. Furthermore, CTBS attenuated EAE-induced glial eN/CD73 expression and activity, while inducing a shift in A2AR expression from glia to neurons, contrary to EAE, where tight coupling of eN/CD73 and A2AR on glial cells is observed. Finally, increased glial A1R expression following CTBS supports anti-inflammatory adenosine actions and potentially contributes to the overall neuroprotective effect observed in EAE animals after CTBS treatment.
T2  - Brain Sciences
T2  - Brain Sciences
T1  - Downregulation of CD73/A2AR-Mediated Adenosine Signaling as a Potential Mechanism of Neuroprotective Effects of Theta-Burst Transcranial Magnetic Stimulation in Acute Experimental Autoimmune Encephalomyelitis
VL  - 11
IS  - 6
SP  - 736
DO  - 10.3390/brainsci11060736
ER  - 

@article{
author = "Dragić, Milorad and Zeljković, Milica and Stevanović, Ivana and Adžić, Marija and Stekić, Anđela and Mihajlović, Katarina and Grković, Ivana and Ilić, Nela and Ilić, Tihomir V. and Nedeljković, Nadežda and Ninković, Milica",
year = "2021",
abstract = "Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by autoimmune-mediated inflammation in the central nervous system. Purinergic signaling is critically involved in MS-associated neuroinflammation and its most widely applied animal model—experimental autoimmune encephalomyelitis (EAE). A promising but poorly understood approach in the treatment of MS is repetitive transcranial magnetic stimulation. In the present study, we aimed to investigate the effect of continuous theta-burst stimulation (CTBS), applied over frontal cranial bone, on the adenosine-mediated signaling system in EAE, particularly on CD73/A2AR/A1R in the context of neuroinflammatory activation of glial cells. EAE was induced in two-month-old female DA rats and in the disease peak treated with CTBS protocol for ten consecutive days. Lumbosacral spinal cord was analyzed immunohistochemically for adenosine-mediated signaling components and pro- and anti-inflammatory factors. We found downregulated IL-1β and NF- κB-ir and upregulated IL-10 pointing towards a reduction in the neuroinflammatory process in EAE animals after CTBS treatment. Furthermore, CTBS attenuated EAE-induced glial eN/CD73 expression and activity, while inducing a shift in A2AR expression from glia to neurons, contrary to EAE, where tight coupling of eN/CD73 and A2AR on glial cells is observed. Finally, increased glial A1R expression following CTBS supports anti-inflammatory adenosine actions and potentially contributes to the overall neuroprotective effect observed in EAE animals after CTBS treatment.",
journal = "Brain Sciences, Brain Sciences",
title = "Downregulation of CD73/A2AR-Mediated Adenosine Signaling as a Potential Mechanism of Neuroprotective Effects of Theta-Burst Transcranial Magnetic Stimulation in Acute Experimental Autoimmune Encephalomyelitis",
volume = "11",
number = "6",
pages = "736",
doi = "10.3390/brainsci11060736"
}

Dragić, M., Zeljković, M., Stevanović, I., Adžić, M., Stekić, A., Mihajlović, K., Grković, I., Ilić, N., Ilić, T. V., Nedeljković, N.,& Ninković, M.. (2021). Downregulation of CD73/A2AR-Mediated Adenosine Signaling as a Potential Mechanism of Neuroprotective Effects of Theta-Burst Transcranial Magnetic Stimulation in Acute Experimental Autoimmune Encephalomyelitis. in Brain Sciences, 11(6), 736.
https://doi.org/10.3390/brainsci11060736

Dragić M, Zeljković M, Stevanović I, Adžić M, Stekić A, Mihajlović K, Grković I, Ilić N, Ilić TV, Nedeljković N, Ninković M. Downregulation of CD73/A2AR-Mediated Adenosine Signaling as a Potential Mechanism of Neuroprotective Effects of Theta-Burst Transcranial Magnetic Stimulation in Acute Experimental Autoimmune Encephalomyelitis. in Brain Sciences. 2021;11(6):736.
doi:10.3390/brainsci11060736 .

Dragić, Milorad, Zeljković, Milica, Stevanović, Ivana, Adžić, Marija, Stekić, Anđela, Mihajlović, Katarina, Grković, Ivana, Ilić, Nela, Ilić, Tihomir V., Nedeljković, Nadežda, Ninković, Milica, "Downregulation of CD73/A2AR-Mediated Adenosine Signaling as a Potential Mechanism of Neuroprotective Effects of Theta-Burst Transcranial Magnetic Stimulation in Acute Experimental Autoimmune Encephalomyelitis" in Brain Sciences, 11, no. 6 (2021):736,
https://doi.org/10.3390/brainsci11060736 . .