Neuroscience 2002 Abstract
| Presentation Number: | 823.18 |
|---|---|
| Abstract Title: | CEP-11004, a Novel Mixed Lineage Kinase Inhibitor, Suppresses Apoptotic Death in Dopamine Neurons of the Substantia Nigra. |
| Authors: |
Ganguly, A. A.*1
; Pratt, R.1
; Oo, T. F.1
; Burke, R. E.1,2
1Neurology, Columbia Univ, New York, NY 2Pathology, Columbia Univ, New York, NY |
| Primary Theme and Topics |
Development - Trophic Factors and Developmental Cell Death -- Trophic factors and cell death |
| Session: |
823. Trophic factors and developmental cell death: trophic factors and neurodegeneration Poster |
| Presentation Time: | Thursday, November 7, 2002 9:00 AM-10:00 AM |
| Location: | Hall A2-B3 B-33 |
| Keywords: | CELL DEATH, PARKINSON, APOPTOSIS, JNK |
Studies have implicated the c-jun N-terminal kinase (JNK) pathway in mediating programmed cell death in neurons. We have previously demonstrated that the protein expression of c-jun and PO4-c-jun is increased in the substantia nigra (SN) following induction of apoptosis by striatal target lesion or by injection of the neurotoxin 6-hydroxydopamine (6OHDA). Nuclear expression of PO4-c-jun is observed in conjunction with apoptotic chromatin clumps in dopamine (DA) neurons suggesting that the JNK pathway may play a role in apoptosis in these neurons. JNK signaling can be mediated through a number of upstream kinases, including the mixed lineage kinase (MLK) family. CEP-11004 is a novel inhibitor of this family and has been shown to attenuate MPTP-mediated elevation in PO4-JNK as well as DA neuronal death (McKenna et al, SFN '01). We have therefore used CEP-11004 to assess the functional role of the MLKs in apoptosis induced in the SN by 6OHDA. CEP-11004 at a dose of 1 mg/kg sc was administered daily from the day prior to the lesion (on postnatal day 6/7) until the animals were sacrificed at postlesion day 6. The number of dopaminergic apoptotic profiles was assessed by cellular and regional criteria as previously defined. There was a 56% decrease in the total number of dopaminergic apoptotic profiles in CEP-treated animals compared to vehicle controls. CEP treatment: 4.0 ± 1.0 (Experimental, E) and 0.3 ± 0.2 (Control, C) sides; Vehicle: 9.1 ± 1.3 (E) and 2.0 ± 0.8 (C) (p<.001, ANOVA; p<.05 CEP E vs Vehicle E, post-hoc). These results suggest that the MLK pathway may play an important role in apoptosis in DA neurons of the SN.
Supported by NS26836, NS 38370, PDF, Lowenstein
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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