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  4. Intracerebroventricular injections of mu-P-75 saporin can produce memory deficits without impairing motor deficits in a mouse model of Alzheimer’s disease.

Intracerebroventricular injections of mu-P-75 saporin can produce memory deficits without impairing motor deficits in a mouse model of Alzheimer’s disease.

Matchynski JJ, Lowrance S, Rossignol J, Puckett N, Derkorver N, Radwan J, Trainor K, Sandstrom M, Dunbar G (2009) Intracerebroventricular injections of mu-P-75 saporin can produce memory deficits without impairing motor deficits in a mouse model of Alzheimer’s disease. Neuroscience 2009 Abstracts 528.1/H34. Society for Neuroscience, Chicago, IL.

Summary: Intracerebroventricular injections of mu-P-75 saporin (Advanced Targeting Systems, San Diego, CA) effectively and efficiently destroys cholinergic neurons and creates memory deficits in mice, mimicking some of the key symptoms of Alzheimer’s disease. Early attempts to use mu-P-75 saporin in mice required a relatively high mean effective dose (ED50) of 3.6 µg in order to create behavioral deficits (Berger-Sweeney et al., 2001, The Journal of Neuroscience, 21: 8164-8173; Hunter et al, 2004, European Journal of Neuroscience, 19: 3305-3316). Recent advances in producing the saporin have lowered the ED50 to doses to 0.4 µg, although the resulting memory deficits are transient, and doses above 0.8 µg can cause motor deficits (Moreau et al., 2008, Hippocampus, 18: 610-622). In an effort to elucidate the behavioral effects of a higher (0.8 µg) dose, we gave bilateral intracerbroventricular injections of mu-P-75 saporin (n=6) or sterile phosphate buffered saline (n=3) into C57/BL6 mice and assessed their cognitive abilities on both a Morris water maze (MWM) and an object-recognition task, while monitoring their motor abilities using a rotarod task. Mice receiving the mu-P-75 saporin performed significantly worse than sham animals on an object recognition task and tended to have longer latencies and swim paths during the seven days of MWM testing. Importantly, no between-group differences were observed for latency to fall on the rotarod task. Collectively, these results suggest that the 0.8 µg dose of saporin is both safe and effective for mimicking AD-like memory deficits, without causing significant motor deficits.

Related Products: mu p75-SAP (Cat. #IT-16)