Neuroscience 2001 Abstract
| Presentation Number: | 234.3 |
|---|---|
| Abstract Title: | 3-NP induced neurotoxicity - assessed by ultra high resolution PET with comparison to MRI and MRS. |
| Authors: |
Brownell, A. L.*1
; Chen, Y. I.1
; Canales, K. E.1
; Livni, E.1
; Powers, R. T.1
; Dedeoglu, A.2
; Beal, F. M.3
; Jenkins, B. G.1
1Radiology, Massachusetts General Hosp, Boston, MA 2Neurology, Massachusetts General Hosp, Boston, MA 3Neurology, Cornell University Medical School, New York, NY |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Neurotoxicity -- Toxic metabolic effects and disorders |
| Secondary Theme and Topics | Neurological and Psychiatric Conditions<br />- Neurodegenerative Disorders<br />-- Excitatory amino acids: exicotoxicity and cell death |
| Session: |
234. Neurotoxicity: toxic metabolites and disorders I Slide |
| Presentation Time: | Monday, November 12, 2001 8:30 AM-8:45 AM |
| Location: | Room 1B |
| Keywords: | neurotoxicity, glucose utilization, dopamine receptors |
3-NP, a succinate dehydrogenase inhibitor, is widely used as an experimental model to study HD, energy metabolism and cell death. We used a rat model to investigate 3-NP induced acute and prolonged neurotoxicity using in vivo imaging of cerebral glucose utilization (CGU)and dopamine receptors by PET, neuroanatomy by MRI and neurochemicals by MRS. 3-NP was administered (male Spraque-Dawley) twice a day (10 mg/kg ip.) until symptomatic or max of 5 days. PET studies of CGU were conducted daily using a super high resolution (1.3x1.3x1.8 mm3) in-house built PET device. MRI and MRS studies were conducted with a GE Omega 4.7 T imager.
Studies of CGU showed significant interanimal variation in the acute response of toxin, similar to motor activity. The average decrease of CGU in the lesions was 31+/-12% and the lesions started to develop on the first day of 3-NP. Four weeks later CGU was recovered to -13+/-5% and then in 3 months decreased again to –48+/-10%. Dopamine D1 and D2 receptors showed progressively decreasing binding by PET after 3-NP using 11C-SCH and 11C-raclopride, respectively. However, the binding of dopamine transporter imaged by 11C-CFT showed early increase (1 week after 3-NP) followed by progressive decrease. MRS showed elevated peaks of lactate and macromolecules as well as succinate immediately after 3-NP toxicity which diminished in 4 months, indicating a reversible process. Choline peak increased and NAA peak decreased in 4 months indicating loss and damage of neurons. Post mortem histological studies confirmed the neural loss.
Studies of CGU showed significant interanimal variation in the acute response of toxin, similar to motor activity. The average decrease of CGU in the lesions was 31+/-12% and the lesions started to develop on the first day of 3-NP. Four weeks later CGU was recovered to -13+/-5% and then in 3 months decreased again to –48+/-10%. Dopamine D1 and D2 receptors showed progressively decreasing binding by PET after 3-NP using 11C-SCH and 11C-raclopride, respectively. However, the binding of dopamine transporter imaged by 11C-CFT showed early increase (1 week after 3-NP) followed by progressive decrease. MRS showed elevated peaks of lactate and macromolecules as well as succinate immediately after 3-NP toxicity which diminished in 4 months, indicating a reversible process. Choline peak increased and NAA peak decreased in 4 months indicating loss and damage of neurons. Post mortem histological studies confirmed the neural loss.
Supported by DAMD17-99-1-9555
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2001 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2001. Online.
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