Aims: GABAergic modulation involved in cognitive processing appears to be substan- tially 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 GABA A 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 trans- genic 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 promi- nent neuroinflammation.
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
AU - Savić, Miroslav
PY - 2022
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4203
AB - Aims: GABAergic modulation involved in cognitive processing appears to be substan- tially 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 GABA A 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 trans- genic 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 promi- nent neuroinflammation.
PB - John Wiley and Sons Inc
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 and Savić, Miroslav",
year = "2022",
abstract = "Aims: GABAergic modulation involved in cognitive processing appears to be substan- tially 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 GABA A 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 trans- genic 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 promi- nent neuroinflammation.",
publisher = "John Wiley and Sons Inc",
journal = "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.,& Savić, 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
John Wiley and Sons Inc., 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 J, Savić 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. 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, Savić, Miroslav, "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 . .
