Targeting activated microglia in Alzheimer's pathology by intraventricular delivery of a phagocytosable MRI contrast agent in APP23 transgenic mice.
The role of phagocytosing immune cells in Alzheimer's pathology can be studied experimentally in APP23 transgenic mice. This present study intended to label phagocytosing immune cells in the plaque periphery of APP23 mice in vivo by intraventricular injection of VSOP-C184, a phagocytosable iron oxide nanoparticle MRI contrast agent. Firstly, the dosages of 0.1, 1.0 and 10 micromol Fe/kg body weight dissolved in 500 nl of artificial cerebrospinal fluid, delivered by stereotaxic surgery were evaluated 4 h after surgery in 7 wild type mice using 7 T MRI. Secondly, the dosage of 1.0 micromol Fe/kg body weight was investigated in 6 APP23 mice. The distribution of iron oxide particles was evaluated histologically. The injection of 0.1 micromol Fe/kg body weight did not result in any signal alterations, 10 micromol resulted in strong signal artifacts. The delivery of 1.0 micromol Fe/kg body weight in wild type mice resulted in MRI signal alterations throughout the ventricular system without large artifacts. It was regarded superior to other dosages for the study of the transgenic mice. There was no difference in MRI signal alterations and the distribution of iron particles in the histology between APP23 and wild type mice using the dosage of 1.0 micromol Fe/kg body weight. Upon intraventricular injection, the phagocytosable contrast agent VSOP-C184 distributes throughout the ventricular system, whereas it does not reach the periphery of amyloid plaques in APP23 mice in a concentration sufficient to cause MRI signal alterations.
Mundt
Adrian P
AP
Center of Neurology, Neurosurgery and Psychiatry, Charité Universitätsmedizin Berlin, Germany.
Winter
Christine
C
Mueller
Susanne
S
Wuerfel
Jens
J
Tysiak
Eva
E
Schnorr
Jörg
J
Taupitz
Matthias
M
Heinz
Andreas
A
Juckel
Georg
G
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D002552:Cerebral Ventricles / Q000378:metabolism / Q000473:pathology; D003287:Contrast Media / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D005290:Ferric Compounds / Q000493:pharmacokinetics*; D007276:Injections, Intraventricular; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology*; D010587:Phagocytosis
D016564:Amyloid beta-Protein Precursor; D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide