Neuroscience 2005 Abstract
| Presentation Number: | 131.8 |
|---|---|
| Abstract Title: | Longitudinal monitoring of motor cortical circuitry in transgenic FALS rats using pharmacologic magnetic resonance imaging. |
| Authors: |
Choi, J.*1
; Jenkins, B. G.1
1Radiology, MGH/HMS, Charlestown, MA |
| Primary Theme and Topics |
Disorders of the Nervous System - Neurodegenerative and Movement Disorders -- ALS: Animal models |
| Session: |
131. ALS: Pathogenesis and Therapeutics Slide |
| Presentation Time: | Sunday, November 13, 2005 9:45 AM-10:00 AM |
| Location: | Washington Convention Center - Room 149A |
| Keywords: |
Introduction - Amyotrophic lateral sclerosis (ALS) is an horrific illness with rapid degeneration of motor neurons. Monitoring motor circuitry in ALS patients is difficult due to the inability of patients to perform even simple motor tasks at later stages. We utilized pharmacologic magnetic resonance imaging (phMRI) of a passive amphetamine challenge for longitudinal study of motor cortex/dopaminergic circuitry in FALS rats.
Methods - Rats expressing SOD1G93A and wild-type (WT) littermates were studied. PhMRI experiments were run using a contrast agent to sensitize images to relative blood volume (rCBV), then amphetamine (2.5 mg/kg, i.v.) was injected. ROI analysis was used to assess regional rCBV changes. Five rats were scanned pre-symptomatically (85+/-28 days) and again after partial hind-limb paralysis (131+/-13 days).
Results - The response to amphetamine produces a pattern that involves sensorimotor cortex (SMCx), caudate/putamen (CPu), and medial prefrontal cortex (MPFCx). The average rCBV (%) in CPu was 16.4+/-2.4 in WT and 20+/-3.3 in pre-symptomatic FALS. In symptomatic FALS this increased to 30.1+/-2.2 (p<0.05). In SMCx the rCBV was 17.2+/-2.5 and 18.4¡Ó3.8 in WT and pre-symptomatic FALS respectively. In symptomatic FALS it decreased to 8.6+/-2.2 (p<0.02). In MPFCx there was no change in peak rCBV, but an increase in FWHM of the rCBV time course from 12.+/-2.7 min to 34.6+/-7.6 min in the symptomatic FALS.
Discussion - Our results can be interpreted as demonstrating a decrease in SMCx activity as a consequence of loss of motor neurons with decreased glutamatergic input to striatum. Decreased glutamatergic input from SMCx would increase dopamine release, and hence, increase rCBV in CPu. These data are compelling in providing a means to assess regional changes in elements of motor circuitry in a manner that is not dependent upon the motor capabilities of the animals. Further, it opens a window on assessment of the longitudinal progression in ALS that is likely to be quite sensitive to therapy. Supported by NIH RO1 DA16187.
Methods - Rats expressing SOD1G93A and wild-type (WT) littermates were studied. PhMRI experiments were run using a contrast agent to sensitize images to relative blood volume (rCBV), then amphetamine (2.5 mg/kg, i.v.) was injected. ROI analysis was used to assess regional rCBV changes. Five rats were scanned pre-symptomatically (85+/-28 days) and again after partial hind-limb paralysis (131+/-13 days).
Results - The response to amphetamine produces a pattern that involves sensorimotor cortex (SMCx), caudate/putamen (CPu), and medial prefrontal cortex (MPFCx). The average rCBV (%) in CPu was 16.4+/-2.4 in WT and 20+/-3.3 in pre-symptomatic FALS. In symptomatic FALS this increased to 30.1+/-2.2 (p<0.05). In SMCx the rCBV was 17.2+/-2.5 and 18.4¡Ó3.8 in WT and pre-symptomatic FALS respectively. In symptomatic FALS it decreased to 8.6+/-2.2 (p<0.02). In MPFCx there was no change in peak rCBV, but an increase in FWHM of the rCBV time course from 12.+/-2.7 min to 34.6+/-7.6 min in the symptomatic FALS.
Discussion - Our results can be interpreted as demonstrating a decrease in SMCx activity as a consequence of loss of motor neurons with decreased glutamatergic input to striatum. Decreased glutamatergic input from SMCx would increase dopamine release, and hence, increase rCBV in CPu. These data are compelling in providing a means to assess regional changes in elements of motor circuitry in a manner that is not dependent upon the motor capabilities of the animals. Further, it opens a window on assessment of the longitudinal progression in ALS that is likely to be quite sensitive to therapy. Supported by NIH RO1 DA16187.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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