![unbiased stereology mouse hippocampus unbiased stereology mouse hippocampus](https://onlinelibrary.wiley.com/cms/asset/ad2c6b19-b322-4458-89c5-a7e613d99540/mfig001.jpg)
The Hippocampal borders were outlined using a 2.5x objective lens. The vessels were visualized using collagen IV-immunostaining that stains the basement membranes of the blood vessels. A random starting section was chosen for each animal. The study used a section interval of six i.e., every sixth section was sampled. The brains were sectioned at 50 microns and underwent shrinkage due to the histological processing to a mean of 18.3 microns, this left enough section thickness for the Spaceballs probe.
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Using Spaceballs, spheres are superimposed on the specimens. This probe uses a shape that is isotropic (a sphere) to obviate the need of proving that the vessels are isotropic or of making the specimens isotropic by vertical or isotropic sectioning. The procedure for Spaceballs is described in the manuscript (Gama Sousa et al., Stereologic Analysis, p. The Spaceballs method (a probe with isotropic virtual spheres) was used to quantify length.
#Unbiased stereology mouse hippocampus software
The Stereo Investigator® software was configured to control a Zeiss microscope outfitted with a motorized XY stage, Z-encoder and camera. Stereo Investigator® was used in this study to perform unbiased stereology to quantify the length and area of blood vessels in, and the volume of, the hippocampus. The authors wanted to know, if and what kind of vascular pathology is present in the hippocampus of mice with the PS1 mutation, and also examine causal relationships between any such vascular pathology and AD by asking what comes first.
#Unbiased stereology mouse hippocampus ps2
CAA occurs when the APP mutation or the PS1 and PS2 mutations together are present, but no CAA has been observed with just PS1. Regarding the inherited disease, three gene mutations in humans have been found to underlie FAD: amyloid precursor protein ( APP), presenilin 1 ( PS1), and presenilin 2 ( PS2). Problems with the sporadic disease also include a decreased density and fragmentation of the microvasculature, and micro-vessels that appear less branched, string-like, and sometimes kinked and looped. Arteries and arterioles that perfuse the arachnoid and pia mater and neocortex are most affected. This vascular pathology is mainly characterized by congophilic amyloid angiopathy (CAA), a deposition of amyloid in the vessel wall. Regarding the sporadic disease, neurofibrillary tangles, and neuron and synapse loss are present in the brain, but there are also vascular abnormalities. The total vascular length was about 45% shorter in the hippocampi of the mice expressing PS1.įAD largely mimics the much more common sporadic disease except for an earlier onset. Unbiased stereology was used to perform quantitative analysis of the length and area of the microvessels in the hippocampus and to determine the volume of the hippocampus. Vessels in cortical and subcortical regions become noticeably thinner and irregular described as string-like, and some become kinked and twisted. Changes in morphometry in the vessels begin when the mice are approximately one year of age. This study addresses age-related, vascular pathology in the brains of mice transfected with a mutated human gene implicated in Familial Alzheimer Disease (FAD), called presenilin 1 (PS1). (2009) Age-Related Vascular Pathology in Transgenic Mice Expressing Presenilin 1-Associated Familial Alzheimer’s Disease Mutations, Am J Pathol. Reviewed paper: Gama Sosa MA, Gasperi RD, Rocher AB, Wang AC, Janssen WG, Flores T, Perez GM, Schmeidler J, Dickstein DL, Hof PR, Elder GA.