Chang, RCC

Hugon, J

So, KF

Suen, KC

Hong Kong Medical Journal

HKU Scholars Hub

Title Reducing calcium-mediated endoplasmic reticulum stress couldattenuate beta-amyloid peptide neurotoxicityAuthor(s) Suen, KC; Hugon, J; So, KF; Chang, RCCCitationThe 8th Medical Research Conference Abstracts, Hong KongMedical Journal, Hong Kong, China, 25-26 January 2003, v. 9 n. 1Supp 1, p. 73Issued Date 2003URL http://hdl.handle.net/10722/45651Rights Creative Commons: Attribution 3.0 Hong Kong LicenseHKMJ Vol 9 No 1 February 2003 Supplement      73Delayed application of GDNF can decrease the NOS expression and rescueinjured motor neurons in adult rat with C7 spinal root avulsionLH Zhou, WT Wu. Department of Anatomy, University of Hong Kong, Hong KongIntroduction: Our previous studies have shown that spinal motoneurons express neuronal NOS and then die fol-lowing root avulsion injury. Expression of nNOS and death of spinal motoneurons due to root avulsion can beprevented if GDNF is applied intrathetically on the lesion site immediately after avulsion. It is unknown whetherdelayed treatment with GDNF could still prevent the death of motoneurons after root avulsion. This hypothesis isexamined in the present study.Method: At 2 weeks after avulsion of C7 spinal root, the laminectomy was made at the C-7 segment and a smallpiece of gelfoam pre-soaked in the solution of 2 microliters normal saline or GDNF at 10 microgram/microliter wasplaced in contact with C7 segment. At different surviving days, the nNOS expression rate and motor neuron sur-vival rate were detected by NADPH-histochemistry and neutral red counter stain.Results: NOS expression rate of the motor neurons was 36.46%, 56.49%, 32.73% or 15.13% at 2 weeks, 3 weeks,4 weeks or 6 weeks after avulsion. With a single dose GDNF, started at 2 weeks after avulsion, the NOS expressionrate was markedly reduced to 7.30%, 7.99% and 9.24% at 3 weeks, 4 weeks or 6 weeks. In lesion animals, themotor neuron survival rate was 85.95%, 80.5%, 59.66% or 36.32% at 2 weeks, 3 weeks, 4 weeks or 6 weeks afteravulsion. But in lesion animals treated with GDNF, the survival rate was increased to 94.33%, 93.75% or 91.83%% at 3 weeks, 4 weeks or 6 weeks.Conclusion: Our data show that during a 6 week process of neurodegeneration a single dose GDNF treatment,though delayed up to 2 weeks, can still inhibit the expression of nNOS and allow substantial rescue of injured motorneurons.Reducing calcium-mediated endoplasmic reticulum stress could attenuate beta-amyloid peptide neurotoxicityKa-Chun Suen, Jacques Hugon, Kwok-Fai So, Raymond Chuen-Chung Chang, Department of Anatomy, Faculty ofMedicine, The University of Hong KongIntroduction: Beta-amyloid peptide (Ab) has been proposed to play an important role in the pathogenesis ofAlzheimer’s disease. Exposure of Abeta could trigger disturbance of cellular calcium homeostasis in cultured neurons.Calcium depletion in the endoplasmic reticulum (ER) is one of the major causes of calcium toxicity. Since Ab couldtrigger ER stress in neurons, we hypothesize that modulation of calcium-mediated ER stress could protect neuronsfrom Abeta neurotoxicity.Methods: Primary cultures of cortical neurons from 17-day-old embryos of Sprague-Dawley rats were set up. Theneurons were pretreated with three ER calcium release modulators, 2-aminoethoxydiphenyl borate (2APB),Xestospongin C (XeC) or FK506 for 2 hours, followed by the treatment with Abeta. In order to assess theirneuroprotective effects against Abeta, the release of lactate dehydrogenase, quantification of apoptotic nuclei stainedwith 4',6'-diamidino-2-phenylindole (DAPI) and assessment of PARP cleavage were examined. Intracellular freecalcium levels, expression of ER stress proteins and caspase-3 activity were also monitored so as to understand themechanism underlying the neuroprotective effects of the three drugs.Results and Conclusion: Our results showed that 2APB, XeC and FK506 significantly attenuated Abetaneurotoxicity. These drugs could reduce calcium depletion-induced ER stress and subsequent caspase-3 activation.Taken together, these results reveal that the modulation of ER calcium release may be a pharmacological target infuture therapeutic approaches of Alzheimer’s diseaseAcknowledgement: This work is supported by Hong Kong Research Grant Council (HKU 7305/00M and HKU7292/02M) to JH and seed funding research grant to RCCC (2001-2002).NUS-03NUS-04

Reducing calcium-mediated endoplasmic reticulum stress could attenuate beta-amyloid peptide neurotoxicity

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Reducing calcium-mediated endoplasmic reticulum stress could attenuate beta-amyloid peptide neurotoxicity

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