3-Nitropropionic acid-induced neurotoxicity--assessed by ultra high resolution positron emission tomography with comparison to magnetic resonance spectroscopy.
To explore acute and long-term effects of 3-nitropropionic acid (3-NP)-induced neurotoxicity, longitudinal positron emission tomography (PET) studies of energy metabolism and magnetic resonance spectroscopic (MRS) studies of neurochemicals were conducted in a rat model. The first injection of 3-NP (20 mg/kg i.p.) was followed by MRS study of neurochemicals and PET study of glucose utilization using [(18)F]2-fluorodeoxy-D-glucose ((18)F-FDG). After that, 3-NP administration was done two times a day with a dose of 10 mg/kg i.p. until animals were symptomatic or for a maximum of 5 days combined with daily PET studies. Long-term effects were investigated 4 weeks and 4 months after cessation of 3-NP. These studies showed a significant inter-animal variation in response of 3-NP toxicity. Animals that developed large striatal lesions had decreased glucose utilization in the striatum and cortex 1 day after starting 3-NP injections. Similarly succinate and lactate/macromolecule levels were enhanced; these changes being, however, reversible. Progressive degeneration was observed by decreasing striatal glucose utilization and N-acetylaspartate (NAA) and increasing choline. These observations paralleled with weight loss and deficits in behavior. Animals that did not develop lesions showed reversible enhancement in cortical glucose utilization and no change in striatal glucose utilization or neurochemicals or locomotor activity.
Brownell
Anna-Liisa
AL
Department of Radiology, Bartlett Hall 504R, Massachusetts General Hospital, Boston, MA 02114, USA. abrownell@partners.org
Chen
Y Iris
YI
Yu
Meixiang
M
Wang
Xukui
X
Dedeoglu
Alpaslan
A
Cicchetti
Francesca
F
Jenkins
Bruce G
BG
Beal
M Flint
MF
D000208:Acute Disease; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D004734:Energy Metabolism / Q000187:drug effects; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism*; D009574:Nitro Compounds; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019802:Succinic Acid / Q000378:metabolism; D014055:Tomography, Emission-Computed / Q000295:instrumentation
D009574:Nitro Compounds; D011422:Propionates; D019788:Fluorodeoxyglucose F18; D019344:Lactic Acid; D019802:Succinic Acid; D005947:Glucose; D002794:Choline; C015392:3-nitropropionic acid