scholarly journals Two-Photon Imaging of Neural Networks in a Mouse Model of Alzheimer's Disease

2011 ◽  
Vol 2011 (10) ◽  
pp. pdb.prot065789-pdb.prot065789 ◽  
Author(s):  
G. Eichhoff ◽  
O. Garaschuk
2018 ◽  
Vol 9 (12) ◽  
pp. 3128-3136 ◽  
Author(s):  
Congping Chen ◽  
Zhuoyi Liang ◽  
Biao Zhou ◽  
Xuesong Li ◽  
Caleb Lui ◽  
...  

2017 ◽  
Vol 114 (47) ◽  
pp. 12384-12389 ◽  
Author(s):  
Jian Yang ◽  
Xueli Zhang ◽  
Peng Yuan ◽  
Jing Yang ◽  
Yungen Xu ◽  
...  

Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder that has a progression that is closely associated with oxidative stress. It has long been speculated that the reactive oxygen species (ROS) level in AD brains is much higher than that in healthy brains. However, evidence from living beings is scarce. Inspired by the “chemistry of glow stick,” we designed a near-IR fluorescence (NIRF) imaging probe, termed CRANAD-61, for sensing ROS to provide evidence at micro- and macrolevels. In CRANAD-61, an oxalate moiety was utilized to react with ROS and to consequentially produce wavelength shifting. Our in vitro data showed that CRANAD-61 was highly sensitive and rapidly responsive to various ROS. On reacting with ROS, its excitation and emission wavelengths significantly shifted to short wavelengths, and this shifting could be harnessed for dual-color two-photon imaging and transformative NIRF imaging. In this report, we showed that CRANAD-61 could be used to identify “active” amyloid beta (Aβ) plaques and cerebral amyloid angiopathy (CAA) surrounded by high ROS levels with two-photon imaging (microlevel) and to provide relative total ROS concentrations in AD brains via whole-brain NIRF imaging (macrolevel). Lastly, we showed that age-related increases in ROS levels in AD brains could be monitored with our NIRF imaging method. We believe that our imaging with CRANAD-61 could provide evidence of ROS at micro- and macrolevels and could be used for monitoring ROS changes under various AD pathological conditions and during drug treatment.


2020 ◽  
Author(s):  
Adham Fani Malekia ◽  
Giulia Cisbania ◽  
Marie-Michèle Plante ◽  
Paul Préfontaine ◽  
Nataly Laflamme ◽  
...  

Abstract Background Muramyl dipeptide (MDP) is a component derived from minimal peptidoglycan motif from bacteria and it is a ligand for the NOD2 receptor. Peripheral administration of MDP converts Ly6Chigh into Ly6Clow monocytes. Previously we have shown that Ly6Clow monocytes play crucial roles in the pathology of a mouse model of Alzheimer’s disease (AD). However, medications with mild immunomodulatory effects that solely target specific monocyte subsets, without triggering microglial activation are rare. Methods 3-months old APPswe/PS1 transgenic male mice and age-matched C57BL/6J mice were used for high frequency (2-times/week) over 6-months and low frequency (once a week) over a 3-months period of intraperitoneally MDP (10 mg/kg) administrations. Flow cytometry analysis of monocyte subsets in blood, behavioral and post mortem analyses were performed. Two-photon microscopy using APP/PS1/CX3CR1gfp/+ mice were conducted to study vascular Aβ clearance by Ly6Clow monocytes upon MDP administration.Results The treatment improved cognitive declines, increased expression levels of postsynaptic density protein 95 (PSD95) andlow density lipoprotein receptor-related protein 1 (LRP1), which are involved in synaptic plasticity and amyloid beta (Aβ) elimination, respectively. In addition, we found monocyte chemoattractant protein-1(MCP-1) levels significantly increased, whereas intercellular adhesion molecule-1(ICAM-1) significantly decreased and microglial marker (Iba1) did not change in treatment group compared to the control. In parallel, we discovered elevated cyclooxygenase-2 (COX2) expression levels in the treated group, which might be a positive factor for synaptic activity. Following MDP treatment, intravital two-photon microscopy demonstrated that Ly6Clow monocytes are recruited into the brain vasculature in APP but not wild type mice, and they are able to pick up Aβ peptides. Conclusions Our results demonstrate that MDP is beneficial in both the early phase and to some extent later phases of the pathology in the mouse model of AD. These data open the way for potential MDP-based medications for AD.


2018 ◽  
Vol 23 (07) ◽  
pp. 1 ◽  
Author(s):  
Patrick Delafontaine-Martel ◽  
Joel Lefebvre ◽  
Pier-Luc Tardif ◽  
Bernard I. Lévy ◽  
Philippe Pouliot ◽  
...  

2014 ◽  
Vol 50 (78) ◽  
pp. 11550-11553 ◽  
Author(s):  
Xueli Zhang ◽  
Yanli Tian ◽  
Peng Yuan ◽  
Yuyan Li ◽  
Mohammad A. Yaseen ◽  
...  

A highly bright bifunctional curcumin analogue CRANAD-28 was designed as a potential theranostic agent for Alzheimer's disease.


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