3-nitropropionic acid-induced changes in bilayer fluidity in synaptosomal membranes: implications for Huntington's disease.
The use of 3-nitropropionic acid (3-NP) and other mitochondria inhibitors to effectuate animal models of Huntington's disease has been well established. 3-NP administration has been shown to lead to pathology similar to that of HD, including massive loss of striatal neurons associated with oxidative stress. Oxidative stress induced by 3-NP also extends to the cortex, an area where little neuron loss occurs. No mechanism as of yet accounts for selective loss of striatal neurons while sparing cortical neurons. In the present study, a nitroxide stearate lipid bilayer-specific spin-label was utilized to probe 3-NP-induced fluidity changes in striatal and cortical synaptosomal membranes. In cortical synaptosomes, membrane fluidity increased in animals previously treated with 3-NP when compared to controls injected with saline vehicle, while in striatal synaptosomes, membrane fluidity decreased in animals treated with 3-NP when compared to controls. The results of the present study suggest that oxidatively-induced changes in membrane fluidity may be involved in mechanisms by which selective striatal neuronal loss occurs in this animal model of Huntington's disease.
Department of Chemistry, Central Connecticut State University, New Britain, Connecticut 06050, USA.
Michael A
MA
LaFontaine
James W
JW
Geddes
D Allan
DA
Butterfield
D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D008051:Lipid Bilayers; D008560:Membrane Fluidity / Q000187:drug effects*; D009574:Nitro Compounds; D018384:Oxidative Stress; D011422:Propionates / Q000494:pharmacology*; D013113:Spin Labels; D013574:Synaptosomes / Q000187:drug effects*
D008051:Lipid Bilayers; D009574:Nitro Compounds; D011422:Propionates; D013113:Spin Labels; C015392:3-nitropropionic acid