Behavioural and anatomical characterisation of the effects of unique human-derived amyloid beta (A&beta) species in mouse brain.Dr David Finkelstein
Neuropathology (Oxidation Disorders Laboratory), Mental Health Research Institute
(03) 9389 2963
dfinkelstein@mhri.edu.au
http://www.mhri.edu.au/dfinkelstein.htmThe cause of cognitive decline in AD has undergone a radical shift in focus over the previous few years. It is now appreciated that there are unique soluble species of the amyloid beta (Aβ) protein that may be crucial to the pathogenesis of the disease. While a limited number of synthetic and in vitro-derived forms of these proteins have been assessed for their behavioural and anatomical effects in animal models, these same species have not yet been isolated from the human brain and then subsequently assessed in vivo.
Aim: To assess the cognitive and anatomical consequences of injecting human-derived soluble A species into the mouse brain.
Methods:
Soluble A peptides will be provided by collaborators. These will be surgically injected into the third ventricle of the normal mouse brain. Following a period of recovery, animals will undergo behavioural characterisation in standard tasks such as the Morris water maze, to assess cognitive function. The anatomical/biochemical effects of these peptides on the brain will also be assessed using a variety of techniques, such as Western blotting and immunohistochemistry.
Relevant Publications. Lesne S, et al. (2006) A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440(7082):352-7.
Townsend M, et al. (2006) Effects of secreted oligomers of amyloid beta-protein on hippocampal synaptic plasticity: a potent role for trimers. J Physiol. 572(Pt 2):477-92. |
