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Effects of agmatine in streptozotocine induced experimental alzheimer model

Year 2013, Volume: 3 Issue: 3, 145 - 153, 30.01.2014

Abstract

Objectives: Alzheimer’s disease is a neurodegenerative disorder characterized by progressive loss of memory followed by complete dementia. Furthermore it is the commonest form of dementia affecting older people. In this study we investigated the role of agmatine (Agm) on learning and memory and on parameters of oxidative stress in intracerebroventricular (i.c.v) streptozotocin (STZ) model of Alzheimer’s disease in rats. 

Materials and Methods: We grouped rats as: naive control, sham operated, STZ and STZ+agmatine. Rats were injected bilaterally i.c.v STZ (3mg/kg) using stereotaxic frame on day 1 and 3 to induce experimental Alzheimer’s disease. After 14 days from 1st STZ injection, learning and memory impairment of rats were observed in passive avoidance. Following this test, agmatine administered intraperitoneal (i.p.) 40mg/kg twice daily for 7 days. These animals were again subjected to these behavioral tests after 7 days agmatine treatment. On the 21st day after 1st STZ injection all groups were sacrificed by decapitation and brain tissues were collected for oxidative stress measurement. Malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase (MPO) activity were measured for estimation of oxidative stress.

Results: In this study it has been demonstrated that i.c.v STZ in Alzheimer model can cause disorder in cognitive functions and oxidative damage. Agmatine treatment is found to be effective to prevent both cognitive deficits as well as the oxidative damage. 

Conclusion: According to results of the current study agmatine, as an endogenous molecule, might be an important modulator in alzheimer’s etiopathogenesis.


Key words: Agmatine, Alzheimer’s disease, intracerebroventricular streptozotocin, oxidative damage, learning and memory

References

  • Sonkusare SK, Kaul CL, Ramarao P Dementia of Alzheimer’s disease and other neurodegenerative disorders—memantine, a new hope. Pharmacol Res. 2005;51(1):1–17.
  • Hooijmans CR, Kiliaan AJ. Fatty acids, lipid metabolism and Alzheimer pathology. Eur J Pharmacol. 2008;585(1):176–196.
  • Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol. 2007;8 (2):101-112.
  • Chong ZZ, Li F, Maiese K. Stress in the brain: Novel cellular mechanisms of injury linked to Alzheimer’s disease. Brain Res Rev. 49(1):1-21. Pratico D. (2008). Oxidative stress hypothesis in Alzheimer’s disease: A reappraisal. Trends Pharmacol Sci. 2005;29(12):609-615.
  • Salminen A, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T. (2009). Inflammation in Alzheimer’s disease: Amyloid-β oligomers trigger innate immunity defence via pattern recognition receptors. Prog Neurobiol. 87(3):181-184.
  • Hynd MR, Scott HL, Dodd PR. Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer's disease. Neurochem Int. 2004;45(5):583-595.
  • Arıcıoğlu F, Regunathan S. Agmatine attenuates stress-and lipopolysaccaride-induced fever in rats. Physiol Behav. 85:370-375. Gilad GM, Salame K, Rabey JM, Gilad VH. (1996). Agmatine treatment is neuroprotective in rodent brain injury models. Life Sci. 2005;58:41-46. Gil-Bea FJ, García-Alloza M, Domínguez J, Marcos B, Ramírez MJ. Evaluation of cholinergic markers in Alzheimer's disease and in a model of cholinergic deficit. Neurosci Lett. 2005;375(1):37-41.
  • Kim JH, Yenari MA, Giffard RG, Cho SW, Park KA, Lee JE. Agmatine reduces infarct area in a mouse model of transient focal cerebral ischemia and protects cultured neurons from ischemia-like injury. Exp. Neurol. 2004;189:122-130.
  • Qiu WW, Zheng RY. Neuroprotective effects of receptor imidazoline 2 and its 109. endogenous ligand agmatine. Neurosci Bull. 2006;22(3):187-191.
  • Galea E, Regunathan S, Eliopoulus V, Feinstein DL, Reis DJ. Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. Biochem J. 1996;316: 247-249.
  • Wang WP, Iyo AH, Miguel-Hidalgo J, Regunathan S, Zhu MY. Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons. Brain Res. 2006;1084(1):210-216.
  • Zhu MY, Piletz JE, Halaris A, Regunathan S. Effect of agmatine against cell death induced by NMDA and glutamate in neurons and PC12 cells. Cell Mol Neurobiol. 2003;23(4-5):865-872.
  • Stewart LS, McKay BE. Acquisition deficit and time-dependent retrograde amnesia for contextual fear conditioning in agmatinetreated rats. Behav Pharmacol. 2000;11(1):93-97.
  • McKay BE, Lado WE, Martin LJ, Galic MA, Fournier NM. Learning and memory in agmatine-treated rats. Pharmacol Biochem Behav. 2002;72(3):551-557.
  • Arteni NS, Lavinsky D, Rodrigues AL, Frison VB, Netto CA. Agmatine facilitates memory of an inhibitory avoidance task in adult rats. Neurobiol Learn Mem. 2002;78(2):465-469.
  • Liu P, Collie ND, Chary S, Jing Y, Zhang H. Spatial learning results in elevated agmatine levels in the rat brain. Hippocampus. 2008;18(11):1094-1098.
  • Liu P, Bergin DH. Differential effects of i.c.v. microinfusion of agmatine on spatial working and reference memory in the rat. Neuroscience. 2009;159(3):951-961.
  • Liu P, Collie ND. Behavioral effects of agmatine in naive rats are taskand delay-dependent. Neurosci. 2009;122(3):557-569.
  • Paxinos G, Watson CR, Emson PC. AChE-stained horizontal sections of the rat brain in stereotaxic coordinates. J Neurosci Methods. 1980;3(2):129-49
  • Sonkusare S, Srinivasan K, Kaul C, Ramarao P. Effect of donepezil and lercanidipine on memory impairment induced by intracerebroventricular streptozotocin in rats. Life Sci. 2005;77(1):1
  • Beutler E. Glutathione in red blood cell metabolism. A manuel of biochemical methods, Grune&Stratton, New York, 1975;112-114.
  • Beuge JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302-310.
  • Hillegas LM, Griswold DE, Brickson B, Albrghtson-Winslow C. Assesment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods. 1990;24:285-295.
  • Liu P, Chary S, Devaraj R, Jing Y, Darlington CL, Smith PF, Tucker IG, Zhang H. Effects of aging on agmatine levels in memory-associated brain structures. Hippocampus. 2008;18(9):853-856.
  • Regunathan S, Feinstein DL, Reis DJ. Anti-proliferative and antiinflammatory actions of imidazoline agents. Are imidazoline receptors involved? Ann NY Acad Sci. 1999;881:410-419.
  • Sastre M, Galea E, Feinstein D, Reis DJ, Regunathan S. Metabolism of agmatine in macrophages: Modulation by lipopolysaccharide and inhibitory cytokines. Biochem J. 1998;330:1405-1409.
  • Horvath G, Kekesi G, Dobos I, Szikszay M, Klimscha W, Benedek G. Effect of agmatine on inflammation-induced thermal hyperalgesia in rats. Eur J Pharmacol. 1999;368:197-204.
  • Regunathan S, Piletz JE. Regulation of inducible nitric oxide synthesis in macrophages and astrocytes. Ann. NY. Acad Sci. 2003;1009:20-29.
  • Satriano J, Schwartz D, Ishizuka S, Lortie MJ, Thomson SC, Gabbai F, Kelly CJ, Blantz RC. Supression of inducible nitric oxide generation by agmatine aldehyde: Benenficial effects in sepsis. J Cell Physiol. 2001;188:313-320.
  • Zhu MY, Wang WP, Cai ZW, Regunathan S, Ordway G. Exogenous agmatine has neuroprotective effects against restraint-induced structural changes in the rat brain. Eur J Neurosci. 2008;27(6):132013
  • Zhu MY, Wang WP, Huang J, Feng YZ, Regunathan S, Bissette G. Repeated immobilization stress alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels. Neurochem Int. 2008;53(6-8):346-354.
  • Kuo JR, Lo CJ, Chio CC, Chang CP, Lin MT. Resuscitation from experimental traumatic brain injury by agmatine therapy. Resuscitation. 2007;75(3):506-514.
  • Sengul G, Takci E, Malcok UA, Akar A, Erdogan F, Kadioglu HH, Aydin IH. A preliminary histopathological study of the effect of agmatine on diffuse brain injury in rats. J Clin Neurosci. 2008;15(10):1125-1129.
  • Hong S, Kim CY, Lee JE, Seong GJ. Agmatine protects cultured retinal ganglion cells from tumor necrosis factor-alpha-induced apoptosis. Life Sci. 2009;84(1-2):28-32.
  • Hong S, Park K, Kim CY, Seong GJ. Agmatine inhibits hypoxiainduced TNF-alpha release from cultured retinal ganglion cells. Biocell. 2008;32(2):201-205.
  • Sugiura T, Kobuchi S, Tsutsui H, Takaoka M, Fujii T, Hayashi K, Matsumura Y. Preventive mechanisms of agmatine against ischemic acute kidney injury in rats. Eur J Pharmacol. 2009;603(1-3):108-113.
  • Sugiura T, Tsutsui H, Takaoka M, Kobuchi S, Hayashi K, Fujii T, Matsumura Y. Protective effect of agmatine on ischemia/reperfusioninduced renal injury in rats. J Cardiovasc Pharmacol. 2008;51(3):2232
  • Lizuka Y, Hong S, Kim CY, Kim SK, Seong GJ. Agmatine pretreatment protects retinal ganglion cells (RGC-5 cell line) from oxidative stress in vitro. Biocell. 2008;32(3):245-250.
  • Lee WT, Hong S, Yoon SH, Kim JH, Park KA, Seong GJ, Lee JE. Neuroprotective effects of agmatine on oxygen-glucose deprived primary-cultured astrocytes and nuclear translocation of nuclear factor-kappa B Brain Res. 2009;1281:64-70.
  • Battaglia V, Rossi CA, Colombatto S, Grillo MA, Toninello A. Different behavior of agmatine in liver mitochondria: inducer of oxidative stress or scavenger of reactive oxygen species? Biochim Biophys Acta. 2007;1768(5):1147-1153.
  • Zhu MY, Wang WP, Huang J, Regunathan S. Chronic treatment with glucocorticoids alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels. J Neurochem. 2007;103(5):1811-1820.

Streptozotosin ile oluşturulan deneysel alzheimer modelinde agmatinin etkilerinin araştırılması

Year 2013, Volume: 3 Issue: 3, 145 - 153, 30.01.2014

Abstract

Amaç: Alzheimer geri dönüşümsüz ve ilerleyici hafıza kaybını takiben tam demansla karakterize nörodejenaratif bir bozukluktur. Yaşlanmayla insanlarda en sık görülen demans formudur. Bu çalışmada sıçanlarda intraserebroventriküler (i.c.v) streptozotosin (STZ) ile oluşturulmuş Alzheimer modelinde agmatinin (Agm) öğrenme ve bellek fonksiyonlarına etkisi ve bu etkinin oksidatif hasar açısından mekanizması araştırılmıştır. 

Gereç ve Yöntem: Çalışmamızda Sprague-Dawley erkek sıçanlar kullanılmış, kontrol, sham opere, STZ ve STZ+Agm olmak üzere 4 gruba ayrılmışlardır. Alzheimer modeli oluşturmak için stereotaksik yöntem ile sıçanlara i.c.v olarak bilateral STZ 3 mg/kg dozda 48 saat arayla 2 defa uygulanmış ve ilk uygulamayı takiben 14 gün beklenmiştir. On beşinci günde pasif sakınma tesi ile öğrenme ve bellek fonksiyonları değerlendirilmiştir. Öğrenmesinin bozulduğu gösterilen sıçanlara 7 gün boyunca günde 2 defa 40mg/kg dozda Agm intraperitoneal (i.p.) olarak uygulanmış ve takiben aynı testler tekrarlanmıştır. Tüm gruplar davranış testleri bittikten sonra (21. günde) dekapite edilerek beyin dokuları toplanmış ve oksidatif hasarı değerlendirmek için malondialdehit (MDA), glutatyon (GSH) seviyeleri ve myeloperoksidaz (MPO) aktivitesi ölçümleri yapılmıştır.

Bulgular: İntraserebroventriküler STZ ile oluşturulmuş alzheimer modelinde kognitif fonksiyonlarında belirgin bozulma olduğu ve bu bozulmaya oksidatif hasarın eşlik ettiği gösterilmiştir. Agmatin tedavisi ile hem kognitif fonksiyon hem de oksidatif hasarı önlemiştir. 

Sonuç: Bu bulgulara dayanarak endojen bir madde olan agmatinin alheimer etyopatogenezinde önemli bir düzenleyici olabileceği düşünülmüştür.


Anahtar Kelimeler : Agmatin, Alzheimer, intraserebroventiküler streptozotosin, oksidatif hasar, öğrenme ve bellek

References

  • Sonkusare SK, Kaul CL, Ramarao P Dementia of Alzheimer’s disease and other neurodegenerative disorders—memantine, a new hope. Pharmacol Res. 2005;51(1):1–17.
  • Hooijmans CR, Kiliaan AJ. Fatty acids, lipid metabolism and Alzheimer pathology. Eur J Pharmacol. 2008;585(1):176–196.
  • Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol. 2007;8 (2):101-112.
  • Chong ZZ, Li F, Maiese K. Stress in the brain: Novel cellular mechanisms of injury linked to Alzheimer’s disease. Brain Res Rev. 49(1):1-21. Pratico D. (2008). Oxidative stress hypothesis in Alzheimer’s disease: A reappraisal. Trends Pharmacol Sci. 2005;29(12):609-615.
  • Salminen A, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T. (2009). Inflammation in Alzheimer’s disease: Amyloid-β oligomers trigger innate immunity defence via pattern recognition receptors. Prog Neurobiol. 87(3):181-184.
  • Hynd MR, Scott HL, Dodd PR. Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer's disease. Neurochem Int. 2004;45(5):583-595.
  • Arıcıoğlu F, Regunathan S. Agmatine attenuates stress-and lipopolysaccaride-induced fever in rats. Physiol Behav. 85:370-375. Gilad GM, Salame K, Rabey JM, Gilad VH. (1996). Agmatine treatment is neuroprotective in rodent brain injury models. Life Sci. 2005;58:41-46. Gil-Bea FJ, García-Alloza M, Domínguez J, Marcos B, Ramírez MJ. Evaluation of cholinergic markers in Alzheimer's disease and in a model of cholinergic deficit. Neurosci Lett. 2005;375(1):37-41.
  • Kim JH, Yenari MA, Giffard RG, Cho SW, Park KA, Lee JE. Agmatine reduces infarct area in a mouse model of transient focal cerebral ischemia and protects cultured neurons from ischemia-like injury. Exp. Neurol. 2004;189:122-130.
  • Qiu WW, Zheng RY. Neuroprotective effects of receptor imidazoline 2 and its 109. endogenous ligand agmatine. Neurosci Bull. 2006;22(3):187-191.
  • Galea E, Regunathan S, Eliopoulus V, Feinstein DL, Reis DJ. Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. Biochem J. 1996;316: 247-249.
  • Wang WP, Iyo AH, Miguel-Hidalgo J, Regunathan S, Zhu MY. Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons. Brain Res. 2006;1084(1):210-216.
  • Zhu MY, Piletz JE, Halaris A, Regunathan S. Effect of agmatine against cell death induced by NMDA and glutamate in neurons and PC12 cells. Cell Mol Neurobiol. 2003;23(4-5):865-872.
  • Stewart LS, McKay BE. Acquisition deficit and time-dependent retrograde amnesia for contextual fear conditioning in agmatinetreated rats. Behav Pharmacol. 2000;11(1):93-97.
  • McKay BE, Lado WE, Martin LJ, Galic MA, Fournier NM. Learning and memory in agmatine-treated rats. Pharmacol Biochem Behav. 2002;72(3):551-557.
  • Arteni NS, Lavinsky D, Rodrigues AL, Frison VB, Netto CA. Agmatine facilitates memory of an inhibitory avoidance task in adult rats. Neurobiol Learn Mem. 2002;78(2):465-469.
  • Liu P, Collie ND, Chary S, Jing Y, Zhang H. Spatial learning results in elevated agmatine levels in the rat brain. Hippocampus. 2008;18(11):1094-1098.
  • Liu P, Bergin DH. Differential effects of i.c.v. microinfusion of agmatine on spatial working and reference memory in the rat. Neuroscience. 2009;159(3):951-961.
  • Liu P, Collie ND. Behavioral effects of agmatine in naive rats are taskand delay-dependent. Neurosci. 2009;122(3):557-569.
  • Paxinos G, Watson CR, Emson PC. AChE-stained horizontal sections of the rat brain in stereotaxic coordinates. J Neurosci Methods. 1980;3(2):129-49
  • Sonkusare S, Srinivasan K, Kaul C, Ramarao P. Effect of donepezil and lercanidipine on memory impairment induced by intracerebroventricular streptozotocin in rats. Life Sci. 2005;77(1):1
  • Beutler E. Glutathione in red blood cell metabolism. A manuel of biochemical methods, Grune&Stratton, New York, 1975;112-114.
  • Beuge JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302-310.
  • Hillegas LM, Griswold DE, Brickson B, Albrghtson-Winslow C. Assesment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods. 1990;24:285-295.
  • Liu P, Chary S, Devaraj R, Jing Y, Darlington CL, Smith PF, Tucker IG, Zhang H. Effects of aging on agmatine levels in memory-associated brain structures. Hippocampus. 2008;18(9):853-856.
  • Regunathan S, Feinstein DL, Reis DJ. Anti-proliferative and antiinflammatory actions of imidazoline agents. Are imidazoline receptors involved? Ann NY Acad Sci. 1999;881:410-419.
  • Sastre M, Galea E, Feinstein D, Reis DJ, Regunathan S. Metabolism of agmatine in macrophages: Modulation by lipopolysaccharide and inhibitory cytokines. Biochem J. 1998;330:1405-1409.
  • Horvath G, Kekesi G, Dobos I, Szikszay M, Klimscha W, Benedek G. Effect of agmatine on inflammation-induced thermal hyperalgesia in rats. Eur J Pharmacol. 1999;368:197-204.
  • Regunathan S, Piletz JE. Regulation of inducible nitric oxide synthesis in macrophages and astrocytes. Ann. NY. Acad Sci. 2003;1009:20-29.
  • Satriano J, Schwartz D, Ishizuka S, Lortie MJ, Thomson SC, Gabbai F, Kelly CJ, Blantz RC. Supression of inducible nitric oxide generation by agmatine aldehyde: Benenficial effects in sepsis. J Cell Physiol. 2001;188:313-320.
  • Zhu MY, Wang WP, Cai ZW, Regunathan S, Ordway G. Exogenous agmatine has neuroprotective effects against restraint-induced structural changes in the rat brain. Eur J Neurosci. 2008;27(6):132013
  • Zhu MY, Wang WP, Huang J, Feng YZ, Regunathan S, Bissette G. Repeated immobilization stress alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels. Neurochem Int. 2008;53(6-8):346-354.
  • Kuo JR, Lo CJ, Chio CC, Chang CP, Lin MT. Resuscitation from experimental traumatic brain injury by agmatine therapy. Resuscitation. 2007;75(3):506-514.
  • Sengul G, Takci E, Malcok UA, Akar A, Erdogan F, Kadioglu HH, Aydin IH. A preliminary histopathological study of the effect of agmatine on diffuse brain injury in rats. J Clin Neurosci. 2008;15(10):1125-1129.
  • Hong S, Kim CY, Lee JE, Seong GJ. Agmatine protects cultured retinal ganglion cells from tumor necrosis factor-alpha-induced apoptosis. Life Sci. 2009;84(1-2):28-32.
  • Hong S, Park K, Kim CY, Seong GJ. Agmatine inhibits hypoxiainduced TNF-alpha release from cultured retinal ganglion cells. Biocell. 2008;32(2):201-205.
  • Sugiura T, Kobuchi S, Tsutsui H, Takaoka M, Fujii T, Hayashi K, Matsumura Y. Preventive mechanisms of agmatine against ischemic acute kidney injury in rats. Eur J Pharmacol. 2009;603(1-3):108-113.
  • Sugiura T, Tsutsui H, Takaoka M, Kobuchi S, Hayashi K, Fujii T, Matsumura Y. Protective effect of agmatine on ischemia/reperfusioninduced renal injury in rats. J Cardiovasc Pharmacol. 2008;51(3):2232
  • Lizuka Y, Hong S, Kim CY, Kim SK, Seong GJ. Agmatine pretreatment protects retinal ganglion cells (RGC-5 cell line) from oxidative stress in vitro. Biocell. 2008;32(3):245-250.
  • Lee WT, Hong S, Yoon SH, Kim JH, Park KA, Seong GJ, Lee JE. Neuroprotective effects of agmatine on oxygen-glucose deprived primary-cultured astrocytes and nuclear translocation of nuclear factor-kappa B Brain Res. 2009;1281:64-70.
  • Battaglia V, Rossi CA, Colombatto S, Grillo MA, Toninello A. Different behavior of agmatine in liver mitochondria: inducer of oxidative stress or scavenger of reactive oxygen species? Biochim Biophys Acta. 2007;1768(5):1147-1153.
  • Zhu MY, Wang WP, Huang J, Regunathan S. Chronic treatment with glucocorticoids alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels. J Neurochem. 2007;103(5):1811-1820.
There are 41 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Müge Şirvancı Yalabık This is me

Özer Şehirli This is me

Tijen Utkan This is me

Feyza Arıcıoğlu

Publication Date January 30, 2014
Submission Date January 30, 2014
Published in Issue Year 2013 Volume: 3 Issue: 3

Cite

APA Şirvancı Yalabık, M., Şehirli, Ö., Utkan, T., Arıcıoğlu, F. (2014). Streptozotosin ile oluşturulan deneysel alzheimer modelinde agmatinin etkilerinin araştırılması. Clinical and Experimental Health Sciences, 3(3), 145-153.
AMA Şirvancı Yalabık M, Şehirli Ö, Utkan T, Arıcıoğlu F. Streptozotosin ile oluşturulan deneysel alzheimer modelinde agmatinin etkilerinin araştırılması. Clinical and Experimental Health Sciences. February 2014;3(3):145-153.
Chicago Şirvancı Yalabık, Müge, Özer Şehirli, Tijen Utkan, and Feyza Arıcıoğlu. “Streptozotosin Ile oluşturulan Deneysel Alzheimer Modelinde Agmatinin Etkilerinin araştırılması”. Clinical and Experimental Health Sciences 3, no. 3 (February 2014): 145-53.
EndNote Şirvancı Yalabık M, Şehirli Ö, Utkan T, Arıcıoğlu F (February 1, 2014) Streptozotosin ile oluşturulan deneysel alzheimer modelinde agmatinin etkilerinin araştırılması. Clinical and Experimental Health Sciences 3 3 145–153.
IEEE M. Şirvancı Yalabık, Ö. Şehirli, T. Utkan, and F. Arıcıoğlu, “Streptozotosin ile oluşturulan deneysel alzheimer modelinde agmatinin etkilerinin araştırılması”, Clinical and Experimental Health Sciences, vol. 3, no. 3, pp. 145–153, 2014.
ISNAD Şirvancı Yalabık, Müge et al. “Streptozotosin Ile oluşturulan Deneysel Alzheimer Modelinde Agmatinin Etkilerinin araştırılması”. Clinical and Experimental Health Sciences 3/3 (February 2014), 145-153.
JAMA Şirvancı Yalabık M, Şehirli Ö, Utkan T, Arıcıoğlu F. Streptozotosin ile oluşturulan deneysel alzheimer modelinde agmatinin etkilerinin araştırılması. Clinical and Experimental Health Sciences. 2014;3:145–153.
MLA Şirvancı Yalabık, Müge et al. “Streptozotosin Ile oluşturulan Deneysel Alzheimer Modelinde Agmatinin Etkilerinin araştırılması”. Clinical and Experimental Health Sciences, vol. 3, no. 3, 2014, pp. 145-53.
Vancouver Şirvancı Yalabık M, Şehirli Ö, Utkan T, Arıcıoğlu F. Streptozotosin ile oluşturulan deneysel alzheimer modelinde agmatinin etkilerinin araştırılması. Clinical and Experimental Health Sciences. 2014;3(3):145-53.

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