Effects of α5 GABAA receptor modulation on social interaction, memory, and neuroinflammation in a mouse model of Alzheimer's disease
Authors
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

Article (Published version)
Metadata
Show full item recordAbstract
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.
Source:
CNS Neuroscience & Therapeutics, 2022, 28, 11, 1767-1778Publisher:
- John Wiley and Sons Inc
Funding / projects:
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200161 (University of Belgrade, Faculty of Pharmacy) (RS-200161)
- NIH for generous financial support (DA- 043204, R01NS076517)
- Milwaukee Institute for Drug Discovery and the University of Wisconsin-Milwaukee's Shimadzu Laboratory
- National Science Foundation, Division of Chemistry [CHE-1625735]
DOI: 10.1111/cns.13914
ISSN: 1755-5930
WoS: 000823616200001
Scopus: 2-s2.0-85134060517
Collections
Institution/Community
PharmacyTY - 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 . .