Neuroscience 2005 Abstract
| Presentation Number: | 385.17 |
|---|---|
| Abstract Title: | Pharmacological manipulation of gliotransmission reduces delayed neuronal death following status epilepticus. |
| Authors: |
Zhu, Y.*1
; Ding, S.1
; Coulter, D. A.2
; Haydon, P. G.1
1Dept Neurosci, Univ. of Pennsylvania, Philadelphia, PA 2PA, 215 Stemmler Hall, 19104-6074, |
| Primary Theme and Topics |
Neural Excitability, Synapses, and Glia: Cellular Mechanisms - Glia-neuron interactions -- Neuron-glial signaling |
| Secondary Theme and Topics | Disorders of the Nervous System<br />- Epilepsy<br />-- Basic mechanisms |
| Session: |
385. Glial--Neuron Signaling I Poster |
| Presentation Time: | Monday, November 14, 2005 8:00 AM-9:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # G6 |
| Keywords: | neurondegeneration, epilepsy, glia, glutamate |
Status epilepticus induces delayed neuronal death whose origins are not clearly defined. Because status epilepticus significantly enhances astrocytic Ca2+ signaling in vivo (See Ding S. et al., SFN abstract 2005), which in turn evokes the release of glutamate, we asked whether pharmacological treatments that impair gliotransmission impact neuronal death. Using Fluoro-Jade B (FJB), a fluorescent marker that specifically stains degenerating neurons, we found that a 1 hr period of pilocarpine-induced status epilepticus caused widespread FJB staining which was otherwise absent in control mice. Since the peak of delayed neuronal death was temporally coincident with enhanced astrocytic Ca2+ signaling we asked whether gliotransmission could contribute to this delayed neuronal death. Administration of the mGluR antagonist MPEP for 3 days reduced astrocytic Ca2+ oscillations and significantly reduced the number of FJB-labeled cells in both the cortex (P<0.05) and hippocampus (P<0.05). Glutamate released from astrocytes acts on ifenprodil-sensitive NMDA receptors (Fellin T.et al., 2004 Neuron; 43(5):729-43) that are known to be coupled to the cell death pathway (Hardingham G.E. et al., Nat Neurosci. 2002; 5(5):405-14). Administration of ifenprodil caused an almost complete blockade of cortical neuronal death (P<0.01) and significantly suppressed delayed death in the hippocampus (P<0.05). By demonstrating reduced neuronal death following pharmacological manipulations that perturb the glutamate-dependent gliotransmission pathway our results raise the possibility that a sustained increase in Ca2+ signaling in astrocytes that is stimulated by status epilepticus contributes to delayed neuronal death through the release of the gliotransmitter glutamate.
Supported by grants from the NIMH and NINDS.
Supported by grants from the NIMH and NINDS.
Supported by NIMH and NINDS
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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