Senescence-associated Beta Galactosidase Expression in Rat Schwann Cells after Chronic Denervation

XIAO Xia, CHEN Ze-ka, DING You-quan. et al

Abstract

To investigate the effect of prolonged axon depletion on senescence-associated beta galactosidase (SA-β-gal) expression in Schwann cells (SCs) of adult rats. Methods Male adult Sprague-Dawley (SD) rats were randomize grouped into sham-operated group and denervation groups for 1 week, 2 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks and 8 weeks. Rats were subjected to right sciatic nerve transection. After particular denervation duration for the distal stumps, animals were anesthetized and perfused. Proximal stumps of 5 mm and distal stumps of 10 mm from injured nerves, and the corresponding segments from the sham groups and contralateral nerves were harvested and prepared for SA-β-gal staining to detect SA-β-gal expression. Then, additional injured distal stumps denervated for 8 weeks were employed for determining cellular distribution of SA-β-gal expression by co-labeling of SA-β-gal and SC-specific protein (S100β). Results SA-β-gal expression transiently increased in distal tips of proximal stumps 2 weeks after adult rat sciatic nerve transection without suture. In contrast, in the distal stumps of transected adult rat sciatic nerves, axon depletion for 2 weeks increased SA-β-gal expression, and the increased expression of SA-β-gal remained constant after prolonged denervation durations. Furthermore, combination of SA-β-gal staining with S100β immunofluorescence staining showed that SA-β-gal expression was exclusively present in denervated SCs. Conclusion Prolonged axon depletion increased SA-β-gal expression in adult rat SCs.

 

Keywords: Chronic denervation, Schwann cell, Cellular senescence, Senescence-associated beta galactosidase, Sciatic nerve transection

 

Full Text:

PDF


References


HOKE A. Mechanisms of Disease: what factors limit the success of peripheral nerve regeneration in humans? Nat Clin Pract Neurol.2006.2(8) :4 18-454.

GORDON T. TYREMAN N. RAJI MA. The basis for diminished functional recovery after delayed peripheral nerve repair. J Neurosci.2011 .31 (14):5325-5334.

GAUDET AD. POPOVICH PG, RAMER MS. Wallerian degeneration; gaining perspective on inflammatory events after peripheral nerve injury. J Neuroinflammation.2011(8): 110. doi: 10.1186/1742-2094-8-110.

SAITO H. KANJE M. DAHLIN LB. Delayed nerve repair increases number of caspase 3 stained Schwann cells. Neurosci Lett. 2009.456(1): 30-33.

HALL SM. The biology of chronically denervated Schwann cells. Ann N Y Acad Sci. 1999 (883): 215-233. 3. doi: 10. 1111/j. 1749-6632. 1999. tb08584. x.

JONSSON S. WI BERG R. MCGRATH AM. Et al. Effect of delayed peripheral nerve repair on nerve regeneration. Schwann cell function and target muscle recovery. PLoS One. 2013. 8(2): e56484. doi: 10. 1371/journal, pone. 0056484.

SAHEB-AL-ZAMAN1 M, YAN Y. FARBER SJ, et al. Limited regeneration in long acellular nerve allografts is associated with increased Schwann cell senescence. Exp Neurol.2013 ( 247 ): 165-177. 4. doi: 10. 1016/j. expneurol. 2013. 04.011.

GOMEZ-SANCHEZ JA, GOMIS-COLOMA C. MOREN1LLA-PALAO C. etal. Epigenetic induction of the Ink4a/Arf locus prevents Schwann cell overproliferation during nerve regeneration and after tumorigenic challenge. Brain. 2013.136(Pt 7): 2262-2278.

ATANASOSKI S. HOLLER D, DK VENTURA L. et al. Cell cycle inhibitors p21 and pi6 are required for the regulation of Schwann cell proliferation, Glia, 2006, 53(2): 147-157.

LEE BY» HAN JA. IM JS. et al. Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging Cell.2006,5(2): 187-195.

YOUNG AR. NARITA M. FERREIRA M, et al. Autophagy mediates the mitotic senescence transition. Genes Dev,2009.23(7):798-803.

IVANOV A. PAWLIKOWSKI J. MANOHARAN I. et al. Lysosome-mediated processing of chromatin in senescence. J Cell Biol,2013,202( 1): 129-143.

KURZDJ, DECARY S, HONG Y, et al. Senescence- associated ( beta )-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J Cell Sci,2000,113(Pt 20),3613-3622.

DE ВАС Q-C H AINIAU X F, KRUSALIMSK Y JD, CAMPIS1 J. et al. Protocols to detect senescence-associated beta- galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo. Nat Protoc, 2009. 4 ( 12): 1798- 1806.

JIANG H. MARTIN V, GOMEZ-MANZANO C, et al. The RB-E2F1 pathway regulates autophagy. Cancer Res, 2010,70(20):7882-7893.

ROD1ER F, CAMPISI J. Four faces of of cellular senescence. J Cell Biol,2001 , 192(4) :547-556.

RUEGER MA, ARAS S. GUNTINAS-IJCHIUS O, et al. Re-activation of atrophic motor Schwann cells after hypoglossal-facial nerve anastomosis. Neurosci 1-ett. 2008, 434(3):253-259 .


Refbacks

  • There are currently no refbacks.