Neuroscience 2004 Abstract
| Presentation Number: | 952.5 |
|---|---|
| Abstract Title: | Targeting phosphate-activated glutaminase impairs glutamatergic synaptic transmission. |
| Authors: |
Lee, S.*1,4
; Chung, W. W.1,6
; Masson, J.7
; Conjard, A.8
; Hamon, M.7
; Hen, R.2,3
; Gingrich, J. A.1,5
; Moore, H.1,6
; Rayport, S.1,2,4
1Psychiatry, Columbia Univ., New York, NY 2Neurobiology & Behavior, Columbia Univ., New York, NY 3Pharmacol., Columbia Univ., New York, NY 4NY, 1051 Riverside Drive NYSPI Unit 62, 10032, 5USA, 1051 Riverside Drive NYSPI Unit 62, 10032, 6Neurosci., 1051 Riverside Drive NYSPI Unit 62, 10032, 7Developmental Psychobiology, 1051 Riverside Drive NYSPI Unit 62, 10032, 8INSERM U288, Clin. Psychobiology, |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Neurotransmitters -- Glutamate |
| Secondary Theme and Topics | Neurological and Psychiatric Conditions<br />- Psychiatric Disorders<br />-- Schizophrenia--Experimental pharmacotherapeutics |
| Session: |
952. Glutamate II Poster |
| Presentation Time: | Wednesday, October 27, 2004 1:00 PM-2:00 PM |
| Location: | San Diego Convention Center - Hall A-H, Board # G31 |
| Keywords: | transgenic mice, microdialysis, glutamate, immunocytochemistry |
Neurotransmitter glutamate (GLU) is thought to derive primarily from the recycling of glutamine to GLU by phosphate-activated glutaminase (PAG). Previously, we reported that mice heterozygous for PAG (PAG-hets) show a 50% reduction in PAG activity, and are sensitized to the stimulant effects of MK-801 (SFN 2003). To examine the impact on GLUergic transmission, we used a monoclonal anti-GLU antibody (Glu2, Diasorin) to visualize GLU distribution; we found that the overall intensity of GLU staining was reduced to about 40%, p = 0.007 in PAG-het cortex. While there was some diminution in cell body labeling, neuropil staining was profoundly diminished, consistent with deficient neurotransmission. GLU microdialysis using the no-net flux method in the anterior cingulate cortex of awake PAG-hets showed that extracellular GLU levels did not differ between controls (0.73 ± 0.19 µM) and PAG-hets (0.70 ± 0.23 µM). Reverse-dialysis of L-trans-pyrrolidine-2,4-dicarboxylate (PDC) consistently increased GLU levels in wild type (WT) mice, while it had an unreliable effect in PAG-hets, showing that there had been a major compensation in GLU reuptake. MK-801 (0.2 mg/kg, i.p.), a manipulation that produces a TTX-dependent — and thus, neuronally-derived — increase in GLU efflux caused almost a doubling of GLU release in WT mice, while it had no effect in PAG-hets. We conclude that PAG is the major source of neurotransmitter GLU, at least in cortex, and that there is relatively little compensation from de novo GLU synthesis.
Supported by NIDA and NARSAD
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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