title: A novel technique for simultaneous bilateral brain infusions in a mouse model of neurodegenerative disease.
abstract: A common problem faced by researchers using transgenic models to study disease is the phenotypic variability that exists within a group or colony of animals. Significant pathological analyses thus often require large numbers of mice to perform. Many lines of transgenic mice harboring the gene for human amyloid precursor protein (APP) with different mutations causing familial Alzheimer's disease have been developed over the past decade to study plaque deposition and other aspects of AD. However, variations in size, density, plaque number, and total amyloid load between animals of the same age and genotype have been identified by our lab and others. Therefore, to study the effects of compounds on amyloid pathology, it was imperative to develop a technique that would allow each brain hemisphere to receive different infusions. We have developed catheters that facilitate simultaneous bilateral infusion in mouse brains, thereby using the contralateral hemisphere of the same animal as an internal control while studying, for example, the effect of compounds on amyloid plaques, a pathological hallmark of the progression of Alzheimer's disease (AD). Several molecules have been identified within the plaques including the major component, the Abeta peptide, and two inflammation-related proteins, apolipoprotein E (apoE) and the serine protease inhibitor alpha-1-antichymotrypsin (ACT). In these experiments, ACT was infused unilaterally over a period of 28 days into the parenchyma and lateral ventricles of PS/APP mice and observed to associate with amyloid plaques, with minimal mortality. Utilizing the ACT/Abeta interaction, details of this procedure are discussed here in detail.
authors.affiliation: USF Byrd Alzheimer's Institute, Tampa, FL 33613, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Bennett
authors.forename: Tim D
authors.initials: TD
authors.lastname: Boyd
authors.forename: Michelle
authors.initials: M
authors.lastname: Norden
authors.forename: Jaya
authors.initials: J
authors.lastname: Padmanabhan
authors.forename: Peter
authors.initials: P
authors.lastname: Neame
authors.forename: Inge
authors.initials: I
authors.lastname: Wefes
authors.forename: Huntington
authors.initials: H
authors.lastname: Potter
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002408:Catheters, Indwelling; D004195:Disease Models, Animal; D004347:Drug Interactions / Q000502:physiology; D004357:Drug Synergism; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D007839:Functional Laterality / Q000502:physiology; D015918:Infusion Pumps, Implantable; D051379:Mice; D008822:Mice, Transgenic; D009480:Neuropharmacology / Q000379:methods*; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015842:Serine Proteinase Inhibitors / Q000378:metabolism / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015842:Serine Proteinase Inhibitors