TY  - JOUR
AU  - Aranđelović, Jovana
AU  - Santrač, Anja
AU  - Batinić, Bojan
AU  - Todorović, Lidija
AU  - Stevanović, Vladimir
AU  - Tiruveedhula, Veera Venkata Naga Phani Babu
AU  - Sharmin, Dishary
AU  - Rashid, Farjana
AU  - Stanojević, Boban
AU  - Cook, James M.
AU  - Savić, Miroslav M.
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10360
AB  - Aims GABAergic modulation involved in cognitive processing appears to be substantially changed in Alzheimer's disease (AD). In a widely used 5xFAD model of AD, we aimed to assess if negative and positive allosteric modulators of α5 GABAA receptors (NAM and PAM, respectively) would affect social interaction, social, object and spatial memory, and neuroinflammation. Methods After 10-day treatment with PAM, NAM, or solvent, 6-month-old transgenic and non-transgenic 5xFAD mice underwent testing in a behavioral battery. Gene expressions of IL-1β, IL-6, TNF-α, GFAP, and IBA-1 were determined in hippocampus and prefrontal cortex by qPCR. Results PAM treatment impaired spatial learning in transgenic females compared to solvent-treated transgenic females, and social recognition in transgenic and non-transgenic males. NAM treatment declined social interaction in transgenic and non-transgenic males, while had beneficial effect on cognitive flexibility in non-transgenic males compared to solvent-treated non-transgenic males. Transgenic animals have not fully displayed cognitive symptoms, but neuroinflammation was confirmed. NAM reduced proinflammatory gene expressions in transgenic females and astrogliosis in transgenic males compared to pathological controls. Conclusion PAM and NAM failed to exert favorable behavioral effects in transgenic animals. Suppression of neuroinflammation obtained with NAM calls for more studies with GABAergic ligands in amyloid beta- and/or tau-dependent models with prominent neuroinflammation.
T2  - CNS Neuroscience & Therapeutics
T2  - CNS Neuroscience & Therapeutics
T1  - Effects of α5 GABAA receptor modulation on social interaction, memory, and neuroinflammation in a mouse model of Alzheimer's disease
VL  - 28
IS  - 11
SP  - 1767
EP  - 1778
DO  - 10.1111/cns.13914
ER  - 

@article{
author = "Aranđelović, Jovana and Santrač, Anja and Batinić, Bojan and Todorović, Lidija and Stevanović, Vladimir and Tiruveedhula, Veera Venkata Naga Phani Babu and Sharmin, Dishary and Rashid, Farjana and Stanojević, Boban and Cook, James M. and Savić, Miroslav M.",
year = "2022",
abstract = "Aims GABAergic modulation involved in cognitive processing appears to be substantially changed in Alzheimer's disease (AD). In a widely used 5xFAD model of AD, we aimed to assess if negative and positive allosteric modulators of α5 GABAA receptors (NAM and PAM, respectively) would affect social interaction, social, object and spatial memory, and neuroinflammation. Methods After 10-day treatment with PAM, NAM, or solvent, 6-month-old transgenic and non-transgenic 5xFAD mice underwent testing in a behavioral battery. Gene expressions of IL-1β, IL-6, TNF-α, GFAP, and IBA-1 were determined in hippocampus and prefrontal cortex by qPCR. Results PAM treatment impaired spatial learning in transgenic females compared to solvent-treated transgenic females, and social recognition in transgenic and non-transgenic males. NAM treatment declined social interaction in transgenic and non-transgenic males, while had beneficial effect on cognitive flexibility in non-transgenic males compared to solvent-treated non-transgenic males. Transgenic animals have not fully displayed cognitive symptoms, but neuroinflammation was confirmed. NAM reduced proinflammatory gene expressions in transgenic females and astrogliosis in transgenic males compared to pathological controls. Conclusion PAM and NAM failed to exert favorable behavioral effects in transgenic animals. Suppression of neuroinflammation obtained with NAM calls for more studies with GABAergic ligands in amyloid beta- and/or tau-dependent models with prominent neuroinflammation.",
journal = "CNS Neuroscience & Therapeutics, CNS Neuroscience & Therapeutics",
title = "Effects of α5 GABAA receptor modulation on social interaction, memory, and neuroinflammation in a mouse model of Alzheimer's disease",
volume = "28",
number = "11",
pages = "1767-1778",
doi = "10.1111/cns.13914"
}

Aranđelović, J., Santrač, A., Batinić, B., Todorović, L., Stevanović, V., Tiruveedhula, V. V. N. P. B., Sharmin, D., Rashid, F., Stanojević, B., Cook, J. M.,& Savić, M. M.. (2022). Effects of α5 GABAA receptor modulation on social interaction, memory, and neuroinflammation in a mouse model of Alzheimer's disease. in CNS Neuroscience & Therapeutics, 28(11), 1767-1778.
https://doi.org/10.1111/cns.13914

Aranđelović J, Santrač A, Batinić B, Todorović L, Stevanović V, Tiruveedhula VVNPB, Sharmin D, Rashid F, Stanojević B, Cook JM, Savić MM. Effects of α5 GABAA receptor modulation on social interaction, memory, and neuroinflammation in a mouse model of Alzheimer's disease. in CNS Neuroscience & Therapeutics. 2022;28(11):1767-1778.
doi:10.1111/cns.13914 .

Aranđelović, Jovana, Santrač, Anja, Batinić, Bojan, Todorović, Lidija, Stevanović, Vladimir, Tiruveedhula, Veera Venkata Naga Phani Babu, Sharmin, Dishary, Rashid, Farjana, Stanojević, Boban, Cook, James M., Savić, Miroslav M., "Effects of α5 GABAA receptor modulation on social interaction, memory, and neuroinflammation in a mouse model of Alzheimer's disease" in CNS Neuroscience & Therapeutics, 28, no. 11 (2022):1767-1778,
https://doi.org/10.1111/cns.13914 . .

TY  - JOUR
AU  - Aranđelović, Jovana
AU  - Santrač, Anja
AU  - Batinić, Bojan
AU  - Todorović, Lidija
AU  - Ahmed Khan, Md Zubair
AU  - Rashid, Farjana
AU  - Poe, Michael M.
AU  - Obradović, Aleksandar
AU  - Cook, James M.
AU  - Savić, Miroslav M.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10072
AB  - Background: Positive and negative allosteric modulators of α5 GABAA receptors (PAM and NAM, respectively) are worthy of investigation as putative treatments of Alzheimer’s disease (AD). However, their potential to modify a dynamic range of behaviors in AD models needs to be systematically examined. Objective: The study aimed to assess effects of MP-III-022 as PAM and PWZ-029 as NAM on emotional reactivity, motivation, and motor function, as well as on gene expression of GABRA2, GABRA3 and GABRA5 subunit of GABAA receptors in prefrontal cortex (PFC) and hippocampus (HC) in 5xFAD mice, as an early-onset transgenic AD model. Methods: The 6-month-old 5xFAD transgenic and non-transgenic mice of both genders underwent a battery of reflexes and behavioral tests (sensorimotor tests, elevated plus maze, and open field) after 10-day intraperitoneal treatment with MP-III-022, PWZ-029, or solvent. The behavioral battery was followed by qPCR analysis of gene expression. Results: MP-III-022 induced a decline in motor function, while PWZ-029 further decreased emotionality of transgenic males, as compared to the transgenic control. No interfering effects on non-cognitive behavior were observed in female mice. In HC, both treatments reversed reciprocal GABRA2 and GABRA3 changes in transgenic females. In PFC, MP-III-022 decreased GABRA5 in both genders, while PWZ-029 increased GABRA2 in male transgenic animals. Conclusion: Gender-dependent protracted effects of PAMs and NAMs in AD model, with detrimental impact on motor capabilities of PAM, and attenuation of emotionality elicited by NAM in transgenic males, were revealed. This favors future research of α5 GABAA receptor modulation in females as more promising.
T2  - Journal of Alzheimer's Disease
T1  - Positive and Negative Selective Allosteric Modulators of α5 GABAA Receptors: Effects on Emotionality, Motivation, and Motor Function in the 5xFAD Model of Alzheimer’s Disease
VL  - 84
IS  - 3
SP  - 1291
EP  - 1302
DO  - 10.3233/JAD-215079
ER  - 

@article{
author = "Aranđelović, Jovana and Santrač, Anja and Batinić, Bojan and Todorović, Lidija and Ahmed Khan, Md Zubair and Rashid, Farjana and Poe, Michael M. and Obradović, Aleksandar and Cook, James M. and Savić, Miroslav M.",
year = "2021",
abstract = "Background: Positive and negative allosteric modulators of α5 GABAA receptors (PAM and NAM, respectively) are worthy of investigation as putative treatments of Alzheimer’s disease (AD). However, their potential to modify a dynamic range of behaviors in AD models needs to be systematically examined. Objective: The study aimed to assess effects of MP-III-022 as PAM and PWZ-029 as NAM on emotional reactivity, motivation, and motor function, as well as on gene expression of GABRA2, GABRA3 and GABRA5 subunit of GABAA receptors in prefrontal cortex (PFC) and hippocampus (HC) in 5xFAD mice, as an early-onset transgenic AD model. Methods: The 6-month-old 5xFAD transgenic and non-transgenic mice of both genders underwent a battery of reflexes and behavioral tests (sensorimotor tests, elevated plus maze, and open field) after 10-day intraperitoneal treatment with MP-III-022, PWZ-029, or solvent. The behavioral battery was followed by qPCR analysis of gene expression. Results: MP-III-022 induced a decline in motor function, while PWZ-029 further decreased emotionality of transgenic males, as compared to the transgenic control. No interfering effects on non-cognitive behavior were observed in female mice. In HC, both treatments reversed reciprocal GABRA2 and GABRA3 changes in transgenic females. In PFC, MP-III-022 decreased GABRA5 in both genders, while PWZ-029 increased GABRA2 in male transgenic animals. Conclusion: Gender-dependent protracted effects of PAMs and NAMs in AD model, with detrimental impact on motor capabilities of PAM, and attenuation of emotionality elicited by NAM in transgenic males, were revealed. This favors future research of α5 GABAA receptor modulation in females as more promising.",
journal = "Journal of Alzheimer's Disease",
title = "Positive and Negative Selective Allosteric Modulators of α5 GABAA Receptors: Effects on Emotionality, Motivation, and Motor Function in the 5xFAD Model of Alzheimer’s Disease",
volume = "84",
number = "3",
pages = "1291-1302",
doi = "10.3233/JAD-215079"
}

Aranđelović, J., Santrač, A., Batinić, B., Todorović, L., Ahmed Khan, M. Z., Rashid, F., Poe, M. M., Obradović, A., Cook, J. M.,& Savić, M. M.. (2021). Positive and Negative Selective Allosteric Modulators of α5 GABAA Receptors: Effects on Emotionality, Motivation, and Motor Function in the 5xFAD Model of Alzheimer’s Disease. in Journal of Alzheimer's Disease, 84(3), 1291-1302.
https://doi.org/10.3233/JAD-215079

Aranđelović J, Santrač A, Batinić B, Todorović L, Ahmed Khan MZ, Rashid F, Poe MM, Obradović A, Cook JM, Savić MM. Positive and Negative Selective Allosteric Modulators of α5 GABAA Receptors: Effects on Emotionality, Motivation, and Motor Function in the 5xFAD Model of Alzheimer’s Disease. in Journal of Alzheimer's Disease. 2021;84(3):1291-1302.
doi:10.3233/JAD-215079 .

Aranđelović, Jovana, Santrač, Anja, Batinić, Bojan, Todorović, Lidija, Ahmed Khan, Md Zubair, Rashid, Farjana, Poe, Michael M., Obradović, Aleksandar, Cook, James M., Savić, Miroslav M., "Positive and Negative Selective Allosteric Modulators of α5 GABAA Receptors: Effects on Emotionality, Motivation, and Motor Function in the 5xFAD Model of Alzheimer’s Disease" in Journal of Alzheimer's Disease, 84, no. 3 (2021):1291-1302,
https://doi.org/10.3233/JAD-215079 . .