TY  - JOUR
AU  - Popović, Marjan
AU  - Stanojević, Željka
AU  - Tosic, Jelena
AU  - Isaković, Aleksandra
AU  - Paunović, Verica
AU  - Petricevic, Sasa
AU  - Martinović, Tamara
AU  - Ciric, Darko
AU  - Kravić-Stevović, Tamara
AU  - Šoškić, Vukić
AU  - Kostić Rajačić, Slađana
AU  - Shakib, Kaveh
AU  - Bumbasirevic, Vladimir
AU  - Trajković, Vladimir
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1812
AB  - Arylpiperazine-based dopaminergic/serotonergic ligands exert neuroprotective activity. We examined the effect of arylpiperazine D-2/5-HT1A ligands, N-{4-[2-(4-phenyl-piperazin-1-yl)-ethyl}-phenyl]- picolinamide (6a) and N-{3-[2-(4-phenyl-piperazin-1-yl)ethyl]- phenyl}-picolinamide (6b), in experimental autoimmune encephalomyelitis (EAE), a model of neuroinflammation. Both compounds (10 mg/kg i.p.) reduced EAE clinical signs in spinal cord homogenate-immunized Dark Agouti rats. Compound 6b was more efficient in delaying the disease onset and reducing the maximal clinical score, which correlated with its higher affinity for D-2 and 5-HT1A receptors. The protectionwas retainedif treatment was limited to the effector (from day 8 onwards), but not the induction phase (day 0-7) of EAE. Compound 6b reduced CNS immune infiltration and expression of mRNA encoding the proinflammatory cytokines tumor necrosis factor, IL-6, IL-1, and GM-CSF, T(H)1 cytokine IFN-gamma, T(H)17 cytokine IL-17, as well as the signature transcription factors of T(H)1 (T-bet) and T(H)17 (ROR gamma t) cells. Arylpiperazine treatment reduced apoptosis and increased the activation of anti-apoptotic mediators Akt and p70S6 kinase in the CNS of EAE animals. The in vitro treatment with 6b protected oligodendrocyte cell line OLN-93 and neuronal cell line PC12 from mitogen-activated normal T cells or myelin basic proteinactivated encephalitogenic T cells. In conclusion, arylpiperazine dopaminergic/serotonergic ligands suppress EAE through a direct neuroprotective action and decrease inCNS inflammation.
PB  - Wiley, Hoboken
T2  - Journal of Neurochemistry
T1  - Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats
VL  - 135
IS  - 1
SP  - 125
EP  - 138
DO  - 10.1111/jnc.13198
ER  - 

@article{
author = "Popović, Marjan and Stanojević, Željka and Tosic, Jelena and Isaković, Aleksandra and Paunović, Verica and Petricevic, Sasa and Martinović, Tamara and Ciric, Darko and Kravić-Stevović, Tamara and Šoškić, Vukić and Kostić Rajačić, Slađana and Shakib, Kaveh and Bumbasirevic, Vladimir and Trajković, Vladimir",
year = "2015",
abstract = "Arylpiperazine-based dopaminergic/serotonergic ligands exert neuroprotective activity. We examined the effect of arylpiperazine D-2/5-HT1A ligands, N-{4-[2-(4-phenyl-piperazin-1-yl)-ethyl}-phenyl]- picolinamide (6a) and N-{3-[2-(4-phenyl-piperazin-1-yl)ethyl]- phenyl}-picolinamide (6b), in experimental autoimmune encephalomyelitis (EAE), a model of neuroinflammation. Both compounds (10 mg/kg i.p.) reduced EAE clinical signs in spinal cord homogenate-immunized Dark Agouti rats. Compound 6b was more efficient in delaying the disease onset and reducing the maximal clinical score, which correlated with its higher affinity for D-2 and 5-HT1A receptors. The protectionwas retainedif treatment was limited to the effector (from day 8 onwards), but not the induction phase (day 0-7) of EAE. Compound 6b reduced CNS immune infiltration and expression of mRNA encoding the proinflammatory cytokines tumor necrosis factor, IL-6, IL-1, and GM-CSF, T(H)1 cytokine IFN-gamma, T(H)17 cytokine IL-17, as well as the signature transcription factors of T(H)1 (T-bet) and T(H)17 (ROR gamma t) cells. Arylpiperazine treatment reduced apoptosis and increased the activation of anti-apoptotic mediators Akt and p70S6 kinase in the CNS of EAE animals. The in vitro treatment with 6b protected oligodendrocyte cell line OLN-93 and neuronal cell line PC12 from mitogen-activated normal T cells or myelin basic proteinactivated encephalitogenic T cells. In conclusion, arylpiperazine dopaminergic/serotonergic ligands suppress EAE through a direct neuroprotective action and decrease inCNS inflammation.",
publisher = "Wiley, Hoboken",
journal = "Journal of Neurochemistry",
title = "Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats",
volume = "135",
number = "1",
pages = "125-138",
doi = "10.1111/jnc.13198"
}

Popović, M., Stanojević, Ž., Tosic, J., Isaković, A., Paunović, V., Petricevic, S., Martinović, T., Ciric, D., Kravić-Stevović, T., Šoškić, V., Kostić Rajačić, S., Shakib, K., Bumbasirevic, V.,& Trajković, V.. (2015). Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats. in Journal of Neurochemistry
Wiley, Hoboken., 135(1), 125-138.
https://doi.org/10.1111/jnc.13198

Popović M, Stanojević Ž, Tosic J, Isaković A, Paunović V, Petricevic S, Martinović T, Ciric D, Kravić-Stevović T, Šoškić V, Kostić Rajačić S, Shakib K, Bumbasirevic V, Trajković V. Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats. in Journal of Neurochemistry. 2015;135(1):125-138.
doi:10.1111/jnc.13198 .

Popović, Marjan, Stanojević, Željka, Tosic, Jelena, Isaković, Aleksandra, Paunović, Verica, Petricevic, Sasa, Martinović, Tamara, Ciric, Darko, Kravić-Stevović, Tamara, Šoškić, Vukić, Kostić Rajačić, Slađana, Shakib, Kaveh, Bumbasirevic, Vladimir, Trajković, Vladimir, "Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats" in Journal of Neurochemistry, 135, no. 1 (2015):125-138,
https://doi.org/10.1111/jnc.13198 . .