Abstract
Taurine is traditionally used to treat Down Syndrome (DS); however, the actual foundation for this treatment is not well understood. DS patients suffer from disturbance of the proteostasis network (PN) due to aberrant calcium signaling, which eventually causes endoplasmic reticulum stress (ERS). Taurine has been suggested to play a role in modulating calcium homeostasis and ERS. This study examined whether taurine affects DS symptoms using C. elegans – a DS model in which calcineurins, Ca2+/calmodulin-dependent protein phosphatase is mutated to null. The DS nematode model has short body length, slow growth, fertility defects, serotonin-resistant egg-laying defects, and faulty thermal sensing. This study focused on whether taurine may ameliorate the severity of DS at the whole-body level, including reduction in ERS. When treated with taurine, DS nematodes appeared to have lower levels of ERS and phenotypes closer to the wild type. DS nematodes also showed improved egg laying efficiency and thermal sensing index comparable to the wild type. Our findings offer a new perspective on the effectiveness of taurine in treating DS and designing therapeutic strategies to lower ERS and restore disrupted PN.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- DS:
-
Down syndrome
- DSCR-1:
-
Down syndrome critical region 1
- RCN:
-
Regulator of calcineurin
- Can a(b):
-
Calcineurin A(B)
- NGM:
-
Nematode growth medium
References
Ahn DH, Singaravelu G, Lee S, Ahnn J, Shim YH (2006) Functional and phenotypic relevance of differentially expressed proteins in calcineurin mutants of Caenorhabditis elegans. Proteomics 6:1340–1350
Aivazidis S, Coughlan CM, Rauniyar AK, Jiang H, Liggett LA, Maclean KN, Roede JR (2017) The burden of trisomy 21 disrupts the proteostasis network in Down syndrome. PLoS One 12(4):e0176307
Bandyopadhyay J, Lee J, Lee J, Lee JI, Yu JR, Jee C, Cho JH, Jung S, Lee MH, Zannoni S, Singson A, Kim DH, Koo HS, Ahnn J (2002) Calcineurin, a calcium/calmodulin-dependent protein phosphatase, is involved in movement, fertility, egg laying, and growth in Caenorhabditis elegans. Mol Biol Cell 13:3281–3293
Bandyopadhyay J, Lee J, Bandyopadhyay A (2004) Regulation of calcineurin, a calcium/calmodulin-dependent protein phosphatase in C. elegans. Mol Cell 18:10–16
Bastiani CA, Gharib S, Simon SMI, Sternberg PW (2003) Caenorhabditis elegans Gal phaq regulates egg-laying behavior via a PLC beta-independent and serotonin-dependent signaling pathway and likely functions both in the nervous system and in muscle. Genetics 165:1805–1822
Baumgartel K, Mansuy IM (2012) Neural functions of calcineurin in synaptic plasticity and memory. Learn Mem 19:375–384
Cuervo AM (2008) Autophagy and aging: keeping that old broomworking. Trends Genet 24:604–612
Di Domenico F, Coccia R, Cocciolo A, Murphy MP, Cenini G, Head E, Butterfield DA, Giorgi A, Schinina ME, Mancuso C, Cini C, Perluigi M (2013) Impairment of proteostasis network in Down syndrome prior to the development of Alzheimer’s disease neuropathology: redox proteomics analysis of human brain. Biochim Biophys Acta 1832(8):1249–1259
Donohoe DR, Jarvis RA, Weeks K, Aamodt EJ, Dwver DS (2009) Behavioral adaptation in C. elegans produced by antipsychotic drugs requires serotonin and is associated with calcium signaling and calcineurin inhibition. Neurosci Res 64:280–289
Dwivedi M, Song HO, Ahnn J (2009) Autophagy genes mediate the effect of calcineurin on life span in C. elegans. Autophagy 5:604–607
Esbensen AJ (2010) Health conditions associated with aging and end of life of adults with Down syndrome. Int Rev Res Ment Retard 39:107–126
Fuentes JJ, Genesca L, Kingsbury TJ, Cunningham KW, Perez-Riba M, Estivill X, dela Luna S (2000) DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineutin-mediated signaling pathways. Hum Mol Genet 9:1681–1690
Hardaker LA, Singer E, Kerr R, Zhou G, Schafer WR (2001) Serotonin modulates locomotory behavior and coordinates egg-laying and movement in Caenorhabditis elegans. Neurobiology 49(4):303–313
Hyun M, Davis K, Lee I, Kim J, Dumur C, You YJ (2016) Fat metabolism regulates satiety behavior in C. elegans. Sci Rep 6:24841
Kaletta T, Hengartner MO (2006) Finding function in novel targets: C. elegans as a model organisms. Nature 5:387–399
Klee CB, Ren H, Wang X (1998) Regulation of the calmodulin-stimulated protein phosphatase calcineurin. J Biol Chem 273:13367–13370
Kuhara A, Inada H, Katsura I, Mori I (2002) Negative regulation and gain control of sensory neurons by the C. elegans calcineurin tax-6. Neuron 33:751–763
Lee MH, Zannoni S, Singson A, Kim DH, Koo HS, Ahnn J (2002) Calcineurin, a calcium/calmodulin-dependent protein phosphatase, is involved in movement, fertility, egg laying, and growthin Caenorhabditis elegans. Mol Biol Cell 13:3281–3293
Lee JI, Dhakal BK, Lee J, Bandyopadhyay J, Jeong SY, Eom SH, Kim DH, Ahnn J (2003) The Caenorhabditis elegans homologue of Down syndrome critical region 1, RCN-1, inhibits multiple functions of the phosphatase calcineurin. J Mol Biol 328:147–156
Lee JI, Mukherjee S, Yoon KH, Dwivedi M, Bandyopadhyay J (2013) The multiple faces of calcineurin signaling in Caenorhabditis elegans: development, behaviour and aging. J Biosci 38:1–15
Palackal T, Moretz R, Wisniewski H, Sturman J (1986) Abnormal visual cortex development in the kitten associated with maternal dietary taurine deprivation. J Neurosci Res 15:223–239
Patterson D (2009) Molecular genetics analysis of Down syndrome. Hum Genet 126:195–214
Strippoli P, Lenzi L, Petrini M, Carinci P, Zannotti M (2000) A new gene family including DSCR1 (Down syndrome critical region 1) and ZAKI-4: characterization from yeast to human and identification of DSCR-1like 2, a novel human member (DSCR1L2). Genomics 64:252–263
Whittle N, Sartori SB, Dlerssen M, Lubec G, Singewald N (2007) Fetal Down syndrome brains exhibit aberrant levels of neurotransmitters critical for normal brain development. Pediatrics 120:e1465–e1471
Yamori Y, Taguchi T, Hamada A, Kunimasa K, Mori H, Mori M (2010) Taurine in health and disease: consistent evidence from experimental and epidemiological studies. J Biomed Sci 17:S6
Yang X, Zhang Z, Feng Y, Ren J, Liu F, Zu T (2012) Effect of taurine on lifespan and antioxidant in Drosophila. Intern Conf Biomed Eng Biotech 206–209
Acknowledgement
This research was supported by the Korea Nazarene University Reseach Grants 2019.Â
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Singapore Pte Ltd.
About this paper
Cite this paper
Chang, H., Lee, D.H. (2019). Pleiotropic Effects of Taurine on Nematode Model for Down Syndrome. In: Hu, J., Piao, F., Schaffer, S., El Idrissi, A., Wu, JY. (eds) Taurine 11. Advances in Experimental Medicine and Biology, vol 1155. Springer, Singapore. https://doi.org/10.1007/978-981-13-8023-5_40
Download citation
DOI: https://doi.org/10.1007/978-981-13-8023-5_40
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-8022-8
Online ISBN: 978-981-13-8023-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)