Chan, YM

Oppenheim, RW

So, KF

Wu, W

Yick, LW

Hong Kong Medical Journal

HKU Scholars Hub

TitleEarly release of mitochondrial cytochrome c and the subsequentactivation of caspase-3 are involved in the apoptotic death ofneonatal motoneurons after injuryAuthor(s) Chan, YM; Yick, LW; So, KF; Oppenheim, RW; Wu, WCitationThe 8th Medical Research Conference, Medical Science Group,The University of Hong Kong, Queen Mary Hospital, Hong Kong,25-26 January 2003, v. 9 n. 1 Suppl, p. 72Issued Date 2003URL http://hdl.handle.net/10722/53980Rights Creative Commons: Attribution 3.0 Hong Kong License72      HKMJ Vol 9 No 1 February 2003 SupplementEarly release of mitochondrial cytochrome c and the subsequent activation ofcaspase-3 are involved in the apoptotic death of neonatal motoneurons after injuryYuen-Man Chan1, Leung-Wah Yick1, Kwok-Fai So1, Ronald W. Oppenheim2 and Wutian Wu1, 1Department of Anatomy,Faculty of Medicine, The University of Hong Kong, Hong Kong and 2Department of Neurobiology and Anatomy and theNeuroscience Program, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.Introduction: We examined the mode of spinal motoneuron (MN) cell death after peripheral nerve injury in neonatalrats.Method: Following root avulsion at C7 spinal segment in neonatal day 1 rats, either PBS or caspase inhibitors wasapplied onto the lesioned area. The postoperative period was 1, 2, 4, 6, 18, 24 and 48 hours. The time course ofapoptosis was assessed by using TUNEL, nuclear staining and expression of cytochrome c and active casapse-3.Results: Apoptotic features were first recognized in degenerating MNs by 6 hours after root avulsion. This wasconfirmed by both TUNEL and nuclear staining. Cytochrome c was released from the mitochondria into the cytosolas early as 1 hour following the lesion. Cytochrome c was localized preferentially in a diffuse pattern 1 hour afterroot avulsion whereas near the plasma membrane in normal motoneurons. By 6 hours after the injury, the activeform of caspase-3 was first visualized by immunohistochemistry. Treatment with a caspase inhibitor Ac-DEVD-CHO could not completely block the activation of caspase-3 and the release of cytochrome c, whereas the adminis-tration of a pan caspase inhibitor Boc-D-FMK delayed the release of cytochrome c for more than 48 hours. Theseresults implied that besides caspase-3, other caspase family members should be taken into account.Conclusion: Because the release of cytochrome c and the activation of caspases play crucial roles in the apoptoticpathway, these results suggest that the mechanism of spinal motoneuron death after root avulsion in developinganimals is apoptotic. Accordingly, inhibition of caspases may be a potentially important mean for rescuing im-mature MNs from injury.Acknowledgement: This work was supported by grants from the Hong Kong Research Grants Council and theUniversity of Hong Kong.Chondroitinase ABC promotes axonal regeneration of Clarke’s neurons beyondthe spinal cord injury scarLeung-Wah Yick1,2, Pik-To Cheung2, Kwok-Fai So1 and Wutian Wu1, 1Department of Anatomy and 2Department ofPaediatrics, Faculty of Medicine, The University of Hong Kong, Hong Kong.Introduction: We have previously shown that enzymatic digestion of chondroitin sulfate proteoglycan (CSPG) atthe injury scar promotes the axonal regeneration of Clarke’s nucleus (CN) neurons into an peripheral nerve graftafter spinal cord hemisection. The present study examined whether digestion of CSPG using chondroitinase ABCpromoted the regeneration of CN neurons across the scar into the rostral spinal cord in neonatal and adult rats.Method: Following hemisection of the spinal cord at T11, either vehicle or chondroitinase ABC was applied ontothe lesion site. The postoperative survival periods were 2 and 4 weeks. Regenerating CN neurons were retrogradelylabeled by Fluoro-Gold injection at spinal cord level C7.Results: In the sham group, there was no regeneration of injured CN neurons in both neonatal and adult rats.Treatment with chondroitinase ABC in neonates resulted in 11.8% and 8.3% of the injured CN neurons regeneratedinto the rostral spinal cord, 2 and 4 weeks respectively. In adults, there were 9.4% and 12.3%, 2 and 4 weeksrespectively, of the injured CN neurons regenerated their axons to the rostral spinal cord. After chondroitinase ABCtreatment, the immunoreactivity for CSPG was dramatically decreased around the lesion site in both neonatal andadult animals.Conclusion: Our results show that degradation of CSPG with chondroitinase ABC can promote the axonalregeneration in the spinal cord. These results further support the hypothesis that CSPG is inhibitory to theregeneration of neurons in the spinal cord after traumatic injury.Acknowledgement: This work was supported by grants from the Hong Kong Research Grants Council and theUniversity of Hong Kong.NUS-01NUS-02

Early release of mitochondrial cytochrome c and the subsequent activation of caspase-3 are involved in the apoptotic death of neonatal motoneurons after injury

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Early release of mitochondrial cytochrome c and the subsequent activation of caspase-3 are involved in the apoptotic death of neonatal motoneurons after injury

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