Imperial College London
Alternate

DrIstvanNagy

Faculty of Medicine, Department of Surgery & Cancer

Reader in Nociceptive Mechanisms
 
 
 
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Contact

 

+44 (0)20 3315 8897i.nagy Website

 
 
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Assistant

 

Miss Steffi Klier +44 (0)20 3315 8816

 
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Location

 

G345Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mirzaei:2021:10.1111/bph.15312,
author = {Mirzaei, N and Mota, B and Birch, A and Davis, N and Romero-Molina, C and Katsouri, L and Palmer, E and Golbano, A and Riggall, L and Nagy, I and Nutt, D and Tyacke, R and Sastre, M},
doi = {10.1111/bph.15312},
journal = {British Journal of Pharmacology},
pages = {654--671},
title = {Imidazoline ligand BU224 reverses cognitive deficits, reduces microgliosis and enhances synaptic connectivity in a mouse model of Alzheimer’s disease},
url = {http://dx.doi.org/10.1111/bph.15312},
volume = {178},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background and PurposeActivation of type2 Imidazoline receptors has been shown to exhibit neuroprotective properties including antiapoptotic and antiinflammatory effects, suggesting a potential therapeutic value in Alzheimer's disease (AD). Here, we explored the effects of the Imidazoline2 ligand BU224 in a model of amyloidosis.Experimental approach6monthold female transgenic 5XFAD and wildtype (WT) mice were treated intraperitoneally with 5 mg.kg1 BU224 or vehicle twice a day for 10 days. Behavioural tests were performed for cognitive functions and neuropathological changes were investigated by immunohistochemistry, Western blot, ELISA and qPCR. Effects of BU224 on APP processing, spine density and calcium imaging were analysed in brain organotypic cultures and N2a cells.Key ResultsBU224 treatment attenuated spatial and perirhinal cortexdependent recognition memory deficits in 5XFAD mice. Fear conditioning testing revealed that BU224 also improved both associative learning and hippocampal and amygdaladependent memory in transgenic but not in WT mice. In the brain, BU224 reduced levels of the microglial marker Iba1 and proinflammatory cytokines IL1β and TNFα, and increased the expression of astrocytic marker GFAP in 5XFAD mice. These beneficial effects were not associated with changes in amyloid pathology, neuronal apoptosis, mitochondrial density, oxidative stress or autophagy markers. Interestingly, ex vivo and in vitro studies suggested that BU224 treatment increased the size of dendritic spines and induced a 3fold reduction in Aβinduced functional changes in NMDA receptors.Conclusions and implicationsOur data indicate that subchronic treatment with BU224 improves memory and reduces inflammation in transgenic AD mice, at stages when animals display severe pathology.
AU  - Mirzaei,N
AU  - Mota,B
AU  - Birch,A
AU  - Davis,N
AU  - Romero-Molina,C
AU  - Katsouri,L
AU  - Palmer,E
AU  - Golbano,A
AU  - Riggall,L
AU  - Nagy,I
AU  - Nutt,D
AU  - Tyacke,R
AU  - Sastre,M
DO  - 10.1111/bph.15312
EP  - 671
PY  - 2021///
SN  - 0007-1188
SP  - 654
TI  - Imidazoline ligand BU224 reverses cognitive deficits, reduces microgliosis and enhances synaptic connectivity in a mouse model of Alzheimer’s disease
T2  - British Journal of Pharmacology
UR  - http://dx.doi.org/10.1111/bph.15312
UR  - https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15312
UR  - http://hdl.handle.net/10044/1/85091
VL  - 178
ER  -
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