The Down-Regulation of Neuroligin-2 and the Correlative Clinical Significance of Serum GABA Over-Expression in Hirschsprung’s Disease

详细信息    查看全文

• 作者：Hongchao Yang (1)
  Jianyi Niu (2)
  Jian Wang (1)
  Fan Zhang (3)
  Qiangye Zhang (1)
  Wentong Zhang (1)
  Aiwu Li (1)
  
• 关键词：Hirschsprung’s disease ; Neuroligin ; 2 gene ; Serum GABA
• 刊名：Neurochemical Research
• 出版年：2014
• 出版时间：August 2014
• 年：2014
• 卷：39
• 期：8
• 页码：1451-1457
• 全文大小：1,130 KB
• 参考文献：1. Roberts RR, Bornstein JC, Bergner AJ, Young HM (2008) Disturbances of colonic motility in mouse models of Hirschsprung’s disease. Am J Physiol Gastrointest Liver Physiol 294(4):996-008
  2. Edery P, Pelet A, Mulligan LM, Abel L, Attié T et al (1994) Long segment and short segment familial Hirschsprung’s disease: variable clinical expression at the RET locus. J Med Genet 31(8):602-06 CrossRef
  3. Heanue TA, Pachnis Vassilis (2007) Enteric nervous system development and Hirschsprung’s disease: advances in genetic and stem cell studies. Nat Rev Neurosci 8(6):466-79 CrossRef
  4. Emison ES, McCallion AS, Kashuk CS (2005) A common sex-dependent mutation in a RET enhancer underliea Hirschsprung disease risk. Nature 434(7035):857-63 CrossRef
  5. Sun M, Xing G, Yuan L, Gan G, Knight D et al (2011) Neuroligin 2 is required for synapse development and function at the drosophila neuromuscular junction. J Neurosci 31(2):687-99 CrossRef
  6. Ichtchenko K, Nguyen T, Sudhof TC (1996) Structures, alternative splicing, andneurexin binding of multiple neuroligins. J Biol Chem 271:2676-682 CrossRef
  7. Siddiqui TJ, Craig AM (2011) Synaptic organizing complexes. Curr Opin Neurobiol 21:132-43 CrossRef
  8. Zhanyan Fu, Vicini Stefano (2009) Neuroligin-2 accelerates GABAergic synapse maturation in cerebellar granule cells. Mol Cell Neurosci 42(1):45-5 CrossRef
  9. Varoqueaux F, Jamain S, Brose N (2004) Neuroligin 2 is exclusively localized to inhibitory synapses. Eur J Cell Biol 83:449-56 CrossRef
  10. Song JY, Ichtchenko K, Sudhof TC, Brose N (1999) Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. Proc Natl Acad Sci USA 96:1100-105 CrossRef
  11. Hoon M, Bauer G, Fritschy JM, Moser T, Falkenburger BH, Varoqueaux F (2009) Neuroligin 2 controls the maturation of GABAergic synapses and information processing in the retina. J Neurosci 29:8039-050 CrossRef
  12. Graf ER, Kang Y, Hauner AM, Craig AM (2006) Structure function and splice site analysis of the synaptogenic activity of the neurexin-1 b LNS domain. J Neurosci 26(16):4256-265 CrossRef
  13. Wouters MM, Boeckxstaens GE (2011) Neuroimmune mechanisms in functional bowel disorders. Neth J Med 69(2):55-1
  14. Wang J, Mou Y, Zhang Q, Zhang F, Yang H et al (2013) Expression and significance of neuroligins in myenteric cells of cajal in Hirschsprung’s disease. PLoS One 8(6):e67205 CrossRef
  15. Zhang Q, Wang J, Li A, Liu H, Zhang W et al (2013) Expression of neurexin and neuroligin in the enteric nervous system and their down-regulated expression levels in Hirschsprung disease. Mol Biol Rep 40(4):2969-975 CrossRef
  16. Chih B, Engelman H, Scheiffele P (2005) Control of excitatory and inhibitory synapse formation by neuroligins. Science 307(5713):1324-328 CrossRef
  17. Graf ER, Zhang X, Jin SX, Linhoff MW, Craig AM (2004) Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell 119(7):1013-026 CrossRef
  18. Levinson JN, El-Husseini A (2005) Building excitatory and inhibitory synapses: balancing neuroligin partnerships. Neuron 48(2):171-74 CrossRef
  19. Prange O, Wong TP, Gerrow K, Wang YT, El-Husseini A (2004) A balance between excitatory and inhibitory synapses is controlled by PSD-95 and neuroligin. Proc Natl Acad Sci USA 101(38):13915-3920 CrossRef
  20. Sudhof TC (2008) Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455(7215):903-11 CrossRef
  21. Biswas S, Reinhard J, Oakeshott J, Russell R, Srinivasan MV et al (2010) Sensory regulation of neuroligins and neurexin I in the honeybee brain. PLoS One 5(2):e9133 CrossRef
  22. Du P, O’Grady G, Davidson JB, Cheng LK, Pullan AJ (2010) Multiscale modeling of gastrointestinal electrophysiology and experimental validation. Crit Rev Biomed Eng 38(3):225-54 CrossRef
  23. Tam PK, Garcia-Barcelo M (2009) Genetic basis of Hirschsprung’s disease. Pediatr Surg Int 25(7):543-58 CrossRef
  24. Amiel J, Sproat-Emison E, Garcia-Barcelo M, Lantieri F, Burzynski G et al (2008) Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet 45(1):1-4 CrossRef
  25. Brooks AS, Bertoli-Avella AM, Burzynski GM, Breedveld GJ, Osinga J et al (2005) Homozygous nonsense mutations in KIAA1279 are associated with malformations of the central and enteric nervous systems. Am J Hum Genet 77(1):120-26 CrossRef
  26. Shimotake T, Tomiyama H, Aoi S, Iwai N (2003) Discrepancy between macroscopic and microscopic transitional zones in Hirschsprung’s disease with reference to the type of RET/GDNF/SOX10 gene mutation. J Pediatr Surg 38(5):698-01 CrossRef
  
• 作者单位：Hongchao Yang (1)
  Jianyi Niu (2)
  Jian Wang (1)
  Fan Zhang (3)
  Qiangye Zhang (1)
  Wentong Zhang (1)
  Aiwu Li (1)
  
  1. Department of Pediatric Surgery, Qilu Hospital, Shandong University, 44#, Wenhua Xi Road, Jinan, 250012, Shandong, People’s Republic of China
  2. Qingzhou Clinical School, Weifang Medical University, Qingzhou, 262500, Shandong, People’s Republic of China
  3. Department of E.N.T, Qilu Hospital, Shandong University, 44#, Wenhua Xi Road, Jinan, 250012, Shandong, People’s Republic of China
  
• ISSN：1573-6903

文摘

The goal of this study was to investigate the expression level of neuroligin-2 in different colon tissue segments of children with Hirschsprung’s disease (HSCR) and the correlative clinical significance of serum Gamma-Aminobutyric Acid (serum GABA) in HSCR. Neuroligin-2 was assessed by Immunohistochemistry staining method on routine paraffin section from different colon tissue segments of HSCR (ganglionic colonic segment, transitional colonic segment and aganglionic colonic segment). Western-blot analysis and real-time fluorescence quantitative PCR(qRT-PCR) were applied to compare and evaluate the expression levels of neuroligin-2 from three segments of HSCR, and we used Enzyme-linked Immunosorbent Assay (ELISA) method to detect and compare the serum GABA between HSCR and non-HSCR. Immunohistochemistry staining demonstrated that intensive neuroligin-2 staining was detected in the ganglion cells in the ganglionic colonic and transitional colonic segments from the HSCR children; however, neuroligin-2 staining was down-regulated significantly in the aganglionic colonic segments. The expression levels of neuroligin-2 mRNA and protein in the aganglionic colonic segment were decreased compared to the ganglionic colonic segment and transitional colonic segment (P?GABA was significantly higher in HSCR than that in non-HSCR. The expression of neuroligin-2 varies from different segments of HSCR. The down-regulation of neuroligin-2 in aganglionic colonic segments may be correlated with the excessive intestine contraction and further result in HSCR. The over-expression of serum GABA may be considered as a new diagnostic method of HSCR.