Araştırma Makalesi
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Deneysel Diyabetin Serebellar CREB / BDNF Yolağı, Oksidatif Stres ve Motor Fonksiyona Etkisi

Yıl 2021, Cilt: 5 Sayı: 3, 248 - 255, 30.12.2021
https://doi.org/10.25048/tudod.976507

Öz

Amaç: Diabetes mellitus (DM), mortalite ve morbidite oranı yüksek olan metabolik bir hastalıktır. DM’nin nörodavranışsal değişikliklere
ve lökomotor aktivitede bozulmaya neden olduğu gösterilmiştir. Siklik AMP Regülatuar Eleman Bağlayıcı Protein (CREB) ve Beyin
kaynaklı nörotrofik faktör (BDNF) proteinleri, beyindeki hafıza, öğrenme ve ruh hâli değişiklikleri gibi sayısız işlevde düzenleyici bir
rol oynar. Bu çalışmanın amacı, deneysel olarak oluşturulan diyabetin serebellum üzerindeki etkilerini, diyabetin serebellar motor
fonksiyonu nasıl etkilediğini ve diyabetin oksidatif stres parametreleri ve sinaptik proteinler üzerindeki etkisini araştırmaktır.
Gereç ve Yöntemler: Bu çalışmada toplam 24 adet erkek Wistar Albino rat (300-350 gr) rastgele olarak Kontrol grubu ve Diabetes
mellitus grubu olmak üzere iki gruba ayrıldı. DM oluşturmak için streptozotosin (STZ) 60 mg/kg tek doz (intraperitoneal) olarak
uygulandı. Açlık kan şekeri, STZ uygulamasından üç gün sonra ölçüldü. Glikoz seviyesi >250 mg/kg olan sıçanlar diyabetik olarak kabul
edildi. Sıçanlarda motor fonksiyonu değerlendirmek için kiriş yürüme testi yapıldı. Serebellum dokusunda CREB/BDNF düzeyleri ELISA
yöntemi ile oksidatif stres parametreleri (Malondialdehit (MDA) ve glutatyon (GSH) düzeyleri) biyokimyasal yöntemle değerlendirildi.
Bulgular: Kiriş yürüme testinde diyabetli grupta platformu geçme süresi kontrol grubuna göre anlamlı derecede daha uzundu (p=0,001).
Serebellum BDNF seviyeleri diyabetik grupta kontrol grubuna göre anlamlı derecede düşük bulundu (p=0,001). Serebellumda CREB ve
GSH düzeyleri gruplar arasında farklı değildi (sırasıyla, p=0,99 p=0,394). Sıçanlarda MDA düzeyleri diyabet grubunda kontrol grubuna
göre daha yüksekti (p=0,001).
Sonuç: Bu çalışma, diyabetin serebellumdaki BDNF düzeylerini azalttığını ve oksidatif stresi artırarak motor fonksiyonların bozulmasına
neden olduğunu göstermiştir.

Destekleyen Kurum

Zonguldak Bülent Ecevit Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Proje Numarası

2017-26259946-02

Teşekkür

Yok

Kaynakça

  • Astrid P, Dirk MW, Ulrich A, Müller R, Landgraf MN, Guido F, Lutz H, Erwin S. Definition, Classification and Diagnosis of Diabetes Mellitus. Exp Clin Endocrinol Diabetes. 2019;127(S 01): S1-S7.
  • Ute Margaretha SG, Ulrich G, Franz K, Tanja G, Sandra H, Irene H, Mellita G, Matthias K, Christoph B, Alexandra KW, Katharina L, Dagmar BT. Gestational Diabetes Mellitus (GDM) – Diagnosis, Treatment and Follow-Up. Guideline of the DDG and DGGG. Geburtshilfe Frauenheilkd. 2018; 78(12): 1219–1231.
  • Cho NH, Shaw JE, Karuranga S, Huang Y, Rocha Fernandes D, Ohlrogge AW, Malanda B. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018; 138:271-281.
  • Joanne BC, Jose CF. Genetics of diabetes mellitus and diabetes complications. Nat Rev Nephrol. 2020;16(7):377-390.
  • Joao RF, Ogurtsova K, Linnenkamp U, Guariguata L, Seuring T, Zhang P, Cavan D, Makaroff LE. IDF Diabetes Atlas estimates of 2014 global health expenditures on diabetes. Diabetes Res Clin Pract. 2016; 117:48-54.
  • Folli F, Corradi D, Fanti P, Davalli A, Paez A, Giaccari A, Perego C, Muscogiuri G. The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro- and macrovascular complications: avenues for a mechanistic-based therapeutic approach. Curr Diabetes Rev. 2011; 7(5):313-24.
  • Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107(9):1058-70.
  • Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414(6865):813-20.
  • Solomon ES, Kuruvilla R. Mechanisms of Neurotrophin Trafficking via Trk Receptors. Mol Cell Neurosci. 2018; 91: 25–33.
  • Widmaier EP, Raff H, Strang KT. Vander İnsan Fizyolojisi (Çev.Ed: Özgünen T) s.174-177 , Güneş Tıp Kitabevi, Ankara, 2014.
  • Schmahmann JD, Sherman JC. Cerebellar cognitive affective syndrome. Int Rev Neurobiol. 1997; 41:433-40.
  • Nakagawa T, Kishino MO, Sugaru E, Yamanaka M, Taiji M, Noguchi H. Brain-derived neurotrophic factor (BDNF) regulates glucose and energy metabolism in diabetic mice. Diabetes Metab Res Rev. 2002;18(3):185-91.
  • Sharma E, Behl T, Mehta V, Kumar A, Setia D, Uddin MS, Zengin G, Arora S. Exploring the various aspects of Brain Derived Neurotropic Factor (BDNF) in Diabetes Mellitus. CNS Neurol Disord Drug Targets 2021;20(1):22-33.
  • Nakagawa T, Tsuchida A, Itakura Y, Nonomura T, Ono M, Hirota F, Inoue T, Nakayama C, Taiji M, Noguchi H. Brain-derived neurotrophic factor regulates glucose metabolism by modulating energy balance in diabetic mice. Diabetes. 2000;49(3):436-44.
  • Fang W, Zhang J, Hong L, Huang W, Dai X, Ye Q, Chen X. Metformin ameliorates stress-induced depression-like behaviors via enhancing the expression of BDNF by activating AMPK/CREB-mediated histone acetylation. J Affect Disord. 2020; 260:302-313.
  • Chaturvedi P, Singh AK, Tiwari V, Thacker AK. J Family Med Prim Care. Diabetes mellitus type 2 impedes functional recovery, neuroplasticity and quality of life after stroke. 2020;9(2): 1035-1041.
  • He M, Wei JX, Mao M, Zhao GY, Tang JJ, Feng S, Lu XM, Wang YT. Synaptic plasticity in PTSD and associated comorbidities: The function and mechanism for diagnostics and therapy. Curr Pharm Des 2018; 24(34):4051-4059.
  • Bathina S, Srinivas N, Das UN. Streptozotocin produces oxidative stress, inflammation and decreases BDNF concentrations to induce apoptosis of RIN5F cells and type 2 diabetes mellitus in Wistar rats. Biochem Biophys Res Commun 2017; 486(2): 406-413.
  • Bathina S, Srinivas N, Das UN. BDNF protects pancreatic β cells (RIN5F) against cytotoxic action of alloxan, streptozotocin, doxorubicin and benzo(a)pyrene in vitro. Metabolism 2016; 65(5): 667-84.
  • Wang L, Hu XH, Huang ZX, Nie Q, Chen ZG, Xiang JW, Qi RL, Yang TH, Xiao Y, Qing WJ, Gigantelli G, Nguyen QD, Li DW. Regulation of CREB Functions by phosphorylation and sumoylation in nervous and visual systems. Curr Mol Med 2017; 16(10): 885-892.
  • Casini AF, Ferrali M, Pompella A, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol 1986;123(3):520-31.
  • Aykaç G, Uysal M, Yalçin AS, Koçak-Toker N, Sivas A, Oz H. The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology 1985;36(1):71-6.
  • Ixchel Osorio-Paz I, Ramírez-Pérez G, Hernández-Ramírez JE, Uribe Carvajal S, Salceda R. Mitochondrial activity in different regions of the brain at the onset of streptozotocin-induced diabetes in rats. Mol Biol Rep 2018; 45(5): 871-879.
  • Rodrigues AF, Biasibetti H, Zanotto BS, Sanches EF, Schmitz F, Nunes VT, Pierozan P, Manfredini V, Magro DDD, Netto CA, Wyse ATS. D-Galactose Causes Motor Coordination Impairment, and Histological and Biochemical Changes in the Cerebellum of Rats. Mol Neurobiol. 2017;54(6): 4127-4137.
  • Nagayach A, Patro N, Patro I. Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function. Front Cell Neurosci. 2014;31;8:355
  • Lunetta M, Damanti AR, Fabbri G, Lombardo M, Di Mauro M, Mughini L. Evidence by magnetic resonance imaging of cerebral alterations of atrophy type in young insulin-dependent diabetic patients J Endocrinol Invest 1994;17: 241-245.
  • Sherif RN. Effect of cerebrolysin on the cerebellum of diabetic rats: An imunohistochemical study. Tissue Cell. 2017;49(6):726-733.
  • Muriach M, Flores-Bellver M, Romero FJ, Barcia JM. Diabetes and the brain: oxidative stress, inflammation, and autophagy. Oxid Med Cell Longev. 2014;2014:102158.
  • Özenoğlu S, Turan İ, Sayan Özaçmak H, Özaçmak VH. Deneysel Diyabet Oluşturulan Sıçanlarda Kalp ve İskelet Kası Nrf2 Yapımı ve Oksidatif Stres Üzerine Melatoninin Etkisinin İncelenmesi. Türk Diyab Obez 2020;1: 46-53.
  • Onar B, Sayan Özaçmak H, Turan İ, Özaçmak VH. Diyabete Bağlı Kognitif Bozukluk Sıçanların Hipokampüslerinde NLRP3 ve Nitrotirozin Seviyelerinin Artışı ile İlişkilidir. Türk Diyab Obez 2019;3: 123-129.
  • Patel SN, Lau-Cam CA. The Effect of Taurine and Its Immediate Homologs on Diabetes-Induced Oxidative Stress in the Brain and Spinal Cord of Rats. Adv Exp Med Biol. 2017;975 Pt 1: 337-351.
  • Catanzaro OL, Capponi JA, Di Martino I, Labal ES, Sirois P. Oxidative stress in the optic nerve and cortical visual area of steptozotocin-induced diabetic Wistar rats: Blockade with a selective bradykinin B (1) receptor antagonist. Neuropeptides. 2017; 66: 97-102.
  • Zhang S, Li H, Zhang L, Li J, Wang R, Wang M. Effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits in the hippocampus of streptozotocin-induced type 1 diabetes mellitus rats. Brain Res. 2017;1657:355-360.
  • Wang M, Yan W, Liu Y, Hu H, Sun Q, Chen X, Zang W, Chen L. Erythropoietin ameliorates diabetes-associated cognitive dysfunction in vitro and in vivo. Sci Rep. 2017;7(1):2801.
  • Xiang Q, Zhang J, Li CY, Wang Y, Zeng MJ, Cai ZX, Tian RB, Jia W, Li XH. Insulin resistance-induced hyperglycemia decreased the activation of Akt/CREB in hippocampus neurons: Molecular evidence for mechanism of diabetes-induced cognitive dysfunction. Neuropeptides. 2015;54: 9-15.
  • Mellesmoen A, Sheeler C, Ferro A, Rainwater O, Cvetanovic M. Brain Derived Neurotrophic Factor (BDNF) Delays Onset of Pathogenesis in Transgenic Mouse Model of Spinocerebellar Ataxia Type 1 (SCA1). Front Cell Neurosci. 2019;12: 509.
  • Inoue T, Ninuma S, Hayashi M, Okuda A, Asaka T, Maejima H. Effects of long-term exercise and low-level inhibition of GABAergic synapses on motor control and the expression of BDNF in the motor related cortex. Neurol Res. 2018;40(1):18-25.
  • Zhong Y, Zhu Y, He T, Li W, Yan H, Miao Y. Rolipram-induced improvement of cognitive function correlates with changes in hippocampal CREB phosphorylation, BDNF and Arc protein levels. Neurosci Lett. 2016;610:171-6.
  • Klintsova AY, Dickson E, Yoshida R, Greenough WT. Altered expression of BDNF and its high-affinity receptor TrkB in response to complex motor learning and moderate exercise. Brain Res. 2004;1028(1):92-104.
  • He YY, Zhang XY, Yung WH, Zhu JN, Wang JJ. Role of BDNF in central motor structures and motor diseases. Mol Neurobiol 2013; 48: 783–793.
  • Grünblatt E, Koutsilieri E, Hoyer S, Riederer P. Gene expression alterations in brain areas of intracerebroventricular streptozotocin treated rat. J Alzheimers Dis. 2006;9(3):261-71.
  • Willson ML, McElnea C, Mariani J, Lohof AM, Sherrard RM. BDNF increases homotypic olivocerebellar reinnervation and associated fine motor and cognitive skill. Brain 2008;131(Pt 4):1099-112.

Effects of Experimental Diabetes on Cerebellar CREB/BDNF Pathway, Oxidative Stress and Motor Function

Yıl 2021, Cilt: 5 Sayı: 3, 248 - 255, 30.12.2021
https://doi.org/10.25048/tudod.976507

Öz

Aim: Diabetes mellitus (DM) is a metabolic disorder with high mortality and morbidity rates. It is shown that DM causes neurobehavioral
changes and locomotor disruption. Cyclic AMP Regulatory Element Binding Protein (CREB) and Brain-derived neurotrophic factor
(BDNF) proteins plays a regulatuar role in numoreus functions in the brain such as memory, learning, and mood changes. The aim of
this study was to investigate the effects of experimentally induced diabetes on cerebellum, how diabetes affects cerebellar motor function
and to investigate the effect of diabetes on oxidative stress parameters and synaptic proteins.
Material and Methods: In this study, a total of 24 male Wistar Albino rats (300-350 g) were divided into two groups as randomly,
Control group and Diabetes mellitus group. Streptozotocin (STZ) was applied as a single 60 mg/kg dose (intraperitoneally) to perform
DM. Fasting blood glucose was measured three days after STZ administration. Rats with a glucose level of >250 mg/kg were considered
diabetic. The beam walking test was performed to evaluate motor function in rat. CREB/BDNF levels were assessed by ELISA method
and oxidative stres parameters (Malondialdehyde (MDA) and glutathione (GSH) levels) were evaluated by biochemical method in uygucerebellum
tissue.
Results: In the beam walking test, the time to cross the platform was significantly longer in the diabetes group compared to the control
group (p=0.001). The levels of BDNF in cerebellum were significantly lower in the diabetic group than in the control group (p=0.001).
The levels of CREB and GSH in cerebellum were not different between the groups (respectively, p=0.99 p=0.394). The levels of MDA
were higher in the diabetes group compared to the control group in the rat (p=0.001).
Conclusion: This study showed that diabetes reduces the levels of BDNF in the cerebellum and increases distortion of motor functions
by increasing oxidative stress.

Proje Numarası

2017-26259946-02

Kaynakça

  • Astrid P, Dirk MW, Ulrich A, Müller R, Landgraf MN, Guido F, Lutz H, Erwin S. Definition, Classification and Diagnosis of Diabetes Mellitus. Exp Clin Endocrinol Diabetes. 2019;127(S 01): S1-S7.
  • Ute Margaretha SG, Ulrich G, Franz K, Tanja G, Sandra H, Irene H, Mellita G, Matthias K, Christoph B, Alexandra KW, Katharina L, Dagmar BT. Gestational Diabetes Mellitus (GDM) – Diagnosis, Treatment and Follow-Up. Guideline of the DDG and DGGG. Geburtshilfe Frauenheilkd. 2018; 78(12): 1219–1231.
  • Cho NH, Shaw JE, Karuranga S, Huang Y, Rocha Fernandes D, Ohlrogge AW, Malanda B. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018; 138:271-281.
  • Joanne BC, Jose CF. Genetics of diabetes mellitus and diabetes complications. Nat Rev Nephrol. 2020;16(7):377-390.
  • Joao RF, Ogurtsova K, Linnenkamp U, Guariguata L, Seuring T, Zhang P, Cavan D, Makaroff LE. IDF Diabetes Atlas estimates of 2014 global health expenditures on diabetes. Diabetes Res Clin Pract. 2016; 117:48-54.
  • Folli F, Corradi D, Fanti P, Davalli A, Paez A, Giaccari A, Perego C, Muscogiuri G. The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro- and macrovascular complications: avenues for a mechanistic-based therapeutic approach. Curr Diabetes Rev. 2011; 7(5):313-24.
  • Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107(9):1058-70.
  • Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414(6865):813-20.
  • Solomon ES, Kuruvilla R. Mechanisms of Neurotrophin Trafficking via Trk Receptors. Mol Cell Neurosci. 2018; 91: 25–33.
  • Widmaier EP, Raff H, Strang KT. Vander İnsan Fizyolojisi (Çev.Ed: Özgünen T) s.174-177 , Güneş Tıp Kitabevi, Ankara, 2014.
  • Schmahmann JD, Sherman JC. Cerebellar cognitive affective syndrome. Int Rev Neurobiol. 1997; 41:433-40.
  • Nakagawa T, Kishino MO, Sugaru E, Yamanaka M, Taiji M, Noguchi H. Brain-derived neurotrophic factor (BDNF) regulates glucose and energy metabolism in diabetic mice. Diabetes Metab Res Rev. 2002;18(3):185-91.
  • Sharma E, Behl T, Mehta V, Kumar A, Setia D, Uddin MS, Zengin G, Arora S. Exploring the various aspects of Brain Derived Neurotropic Factor (BDNF) in Diabetes Mellitus. CNS Neurol Disord Drug Targets 2021;20(1):22-33.
  • Nakagawa T, Tsuchida A, Itakura Y, Nonomura T, Ono M, Hirota F, Inoue T, Nakayama C, Taiji M, Noguchi H. Brain-derived neurotrophic factor regulates glucose metabolism by modulating energy balance in diabetic mice. Diabetes. 2000;49(3):436-44.
  • Fang W, Zhang J, Hong L, Huang W, Dai X, Ye Q, Chen X. Metformin ameliorates stress-induced depression-like behaviors via enhancing the expression of BDNF by activating AMPK/CREB-mediated histone acetylation. J Affect Disord. 2020; 260:302-313.
  • Chaturvedi P, Singh AK, Tiwari V, Thacker AK. J Family Med Prim Care. Diabetes mellitus type 2 impedes functional recovery, neuroplasticity and quality of life after stroke. 2020;9(2): 1035-1041.
  • He M, Wei JX, Mao M, Zhao GY, Tang JJ, Feng S, Lu XM, Wang YT. Synaptic plasticity in PTSD and associated comorbidities: The function and mechanism for diagnostics and therapy. Curr Pharm Des 2018; 24(34):4051-4059.
  • Bathina S, Srinivas N, Das UN. Streptozotocin produces oxidative stress, inflammation and decreases BDNF concentrations to induce apoptosis of RIN5F cells and type 2 diabetes mellitus in Wistar rats. Biochem Biophys Res Commun 2017; 486(2): 406-413.
  • Bathina S, Srinivas N, Das UN. BDNF protects pancreatic β cells (RIN5F) against cytotoxic action of alloxan, streptozotocin, doxorubicin and benzo(a)pyrene in vitro. Metabolism 2016; 65(5): 667-84.
  • Wang L, Hu XH, Huang ZX, Nie Q, Chen ZG, Xiang JW, Qi RL, Yang TH, Xiao Y, Qing WJ, Gigantelli G, Nguyen QD, Li DW. Regulation of CREB Functions by phosphorylation and sumoylation in nervous and visual systems. Curr Mol Med 2017; 16(10): 885-892.
  • Casini AF, Ferrali M, Pompella A, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol 1986;123(3):520-31.
  • Aykaç G, Uysal M, Yalçin AS, Koçak-Toker N, Sivas A, Oz H. The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology 1985;36(1):71-6.
  • Ixchel Osorio-Paz I, Ramírez-Pérez G, Hernández-Ramírez JE, Uribe Carvajal S, Salceda R. Mitochondrial activity in different regions of the brain at the onset of streptozotocin-induced diabetes in rats. Mol Biol Rep 2018; 45(5): 871-879.
  • Rodrigues AF, Biasibetti H, Zanotto BS, Sanches EF, Schmitz F, Nunes VT, Pierozan P, Manfredini V, Magro DDD, Netto CA, Wyse ATS. D-Galactose Causes Motor Coordination Impairment, and Histological and Biochemical Changes in the Cerebellum of Rats. Mol Neurobiol. 2017;54(6): 4127-4137.
  • Nagayach A, Patro N, Patro I. Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function. Front Cell Neurosci. 2014;31;8:355
  • Lunetta M, Damanti AR, Fabbri G, Lombardo M, Di Mauro M, Mughini L. Evidence by magnetic resonance imaging of cerebral alterations of atrophy type in young insulin-dependent diabetic patients J Endocrinol Invest 1994;17: 241-245.
  • Sherif RN. Effect of cerebrolysin on the cerebellum of diabetic rats: An imunohistochemical study. Tissue Cell. 2017;49(6):726-733.
  • Muriach M, Flores-Bellver M, Romero FJ, Barcia JM. Diabetes and the brain: oxidative stress, inflammation, and autophagy. Oxid Med Cell Longev. 2014;2014:102158.
  • Özenoğlu S, Turan İ, Sayan Özaçmak H, Özaçmak VH. Deneysel Diyabet Oluşturulan Sıçanlarda Kalp ve İskelet Kası Nrf2 Yapımı ve Oksidatif Stres Üzerine Melatoninin Etkisinin İncelenmesi. Türk Diyab Obez 2020;1: 46-53.
  • Onar B, Sayan Özaçmak H, Turan İ, Özaçmak VH. Diyabete Bağlı Kognitif Bozukluk Sıçanların Hipokampüslerinde NLRP3 ve Nitrotirozin Seviyelerinin Artışı ile İlişkilidir. Türk Diyab Obez 2019;3: 123-129.
  • Patel SN, Lau-Cam CA. The Effect of Taurine and Its Immediate Homologs on Diabetes-Induced Oxidative Stress in the Brain and Spinal Cord of Rats. Adv Exp Med Biol. 2017;975 Pt 1: 337-351.
  • Catanzaro OL, Capponi JA, Di Martino I, Labal ES, Sirois P. Oxidative stress in the optic nerve and cortical visual area of steptozotocin-induced diabetic Wistar rats: Blockade with a selective bradykinin B (1) receptor antagonist. Neuropeptides. 2017; 66: 97-102.
  • Zhang S, Li H, Zhang L, Li J, Wang R, Wang M. Effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits in the hippocampus of streptozotocin-induced type 1 diabetes mellitus rats. Brain Res. 2017;1657:355-360.
  • Wang M, Yan W, Liu Y, Hu H, Sun Q, Chen X, Zang W, Chen L. Erythropoietin ameliorates diabetes-associated cognitive dysfunction in vitro and in vivo. Sci Rep. 2017;7(1):2801.
  • Xiang Q, Zhang J, Li CY, Wang Y, Zeng MJ, Cai ZX, Tian RB, Jia W, Li XH. Insulin resistance-induced hyperglycemia decreased the activation of Akt/CREB in hippocampus neurons: Molecular evidence for mechanism of diabetes-induced cognitive dysfunction. Neuropeptides. 2015;54: 9-15.
  • Mellesmoen A, Sheeler C, Ferro A, Rainwater O, Cvetanovic M. Brain Derived Neurotrophic Factor (BDNF) Delays Onset of Pathogenesis in Transgenic Mouse Model of Spinocerebellar Ataxia Type 1 (SCA1). Front Cell Neurosci. 2019;12: 509.
  • Inoue T, Ninuma S, Hayashi M, Okuda A, Asaka T, Maejima H. Effects of long-term exercise and low-level inhibition of GABAergic synapses on motor control and the expression of BDNF in the motor related cortex. Neurol Res. 2018;40(1):18-25.
  • Zhong Y, Zhu Y, He T, Li W, Yan H, Miao Y. Rolipram-induced improvement of cognitive function correlates with changes in hippocampal CREB phosphorylation, BDNF and Arc protein levels. Neurosci Lett. 2016;610:171-6.
  • Klintsova AY, Dickson E, Yoshida R, Greenough WT. Altered expression of BDNF and its high-affinity receptor TrkB in response to complex motor learning and moderate exercise. Brain Res. 2004;1028(1):92-104.
  • He YY, Zhang XY, Yung WH, Zhu JN, Wang JJ. Role of BDNF in central motor structures and motor diseases. Mol Neurobiol 2013; 48: 783–793.
  • Grünblatt E, Koutsilieri E, Hoyer S, Riederer P. Gene expression alterations in brain areas of intracerebroventricular streptozotocin treated rat. J Alzheimers Dis. 2006;9(3):261-71.
  • Willson ML, McElnea C, Mariani J, Lohof AM, Sherrard RM. BDNF increases homotypic olivocerebellar reinnervation and associated fine motor and cognitive skill. Brain 2008;131(Pt 4):1099-112.
Toplam 42 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma Makalesi
Yazarlar

Birgül Altuğ Bu kişi benim 0000-0002-4193-4219

İnci Turan 0000-0003-2211-3914

Hale Sayan Özaçmak 0000-0002-3564-0468

Veysel Haktan Özaçmak 0000-0003-2651-8353

Proje Numarası 2017-26259946-02
Yayımlanma Tarihi 30 Aralık 2021
Kabul Tarihi 14 Aralık 2021
Yayımlandığı Sayı Yıl 2021 Cilt: 5 Sayı: 3

Kaynak Göster

APA Altuğ, B., Turan, İ., Sayan Özaçmak, H., Özaçmak, V. H. (2021). Deneysel Diyabetin Serebellar CREB / BDNF Yolağı, Oksidatif Stres ve Motor Fonksiyona Etkisi. Türkiye Diyabet Ve Obezite Dergisi, 5(3), 248-255. https://doi.org/10.25048/tudod.976507
AMA Altuğ B, Turan İ, Sayan Özaçmak H, Özaçmak VH. Deneysel Diyabetin Serebellar CREB / BDNF Yolağı, Oksidatif Stres ve Motor Fonksiyona Etkisi. Turk J Diab Obes. Aralık 2021;5(3):248-255. doi:10.25048/tudod.976507
Chicago Altuğ, Birgül, İnci Turan, Hale Sayan Özaçmak, ve Veysel Haktan Özaçmak. “Deneysel Diyabetin Serebellar CREB / BDNF Yolağı, Oksidatif Stres Ve Motor Fonksiyona Etkisi”. Türkiye Diyabet Ve Obezite Dergisi 5, sy. 3 (Aralık 2021): 248-55. https://doi.org/10.25048/tudod.976507.
EndNote Altuğ B, Turan İ, Sayan Özaçmak H, Özaçmak VH (01 Aralık 2021) Deneysel Diyabetin Serebellar CREB / BDNF Yolağı, Oksidatif Stres ve Motor Fonksiyona Etkisi. Türkiye Diyabet ve Obezite Dergisi 5 3 248–255.
IEEE B. Altuğ, İ. Turan, H. Sayan Özaçmak, ve V. H. Özaçmak, “Deneysel Diyabetin Serebellar CREB / BDNF Yolağı, Oksidatif Stres ve Motor Fonksiyona Etkisi”, Turk J Diab Obes, c. 5, sy. 3, ss. 248–255, 2021, doi: 10.25048/tudod.976507.
ISNAD Altuğ, Birgül vd. “Deneysel Diyabetin Serebellar CREB / BDNF Yolağı, Oksidatif Stres Ve Motor Fonksiyona Etkisi”. Türkiye Diyabet ve Obezite Dergisi 5/3 (Aralık 2021), 248-255. https://doi.org/10.25048/tudod.976507.
JAMA Altuğ B, Turan İ, Sayan Özaçmak H, Özaçmak VH. Deneysel Diyabetin Serebellar CREB / BDNF Yolağı, Oksidatif Stres ve Motor Fonksiyona Etkisi. Turk J Diab Obes. 2021;5:248–255.
MLA Altuğ, Birgül vd. “Deneysel Diyabetin Serebellar CREB / BDNF Yolağı, Oksidatif Stres Ve Motor Fonksiyona Etkisi”. Türkiye Diyabet Ve Obezite Dergisi, c. 5, sy. 3, 2021, ss. 248-55, doi:10.25048/tudod.976507.
Vancouver Altuğ B, Turan İ, Sayan Özaçmak H, Özaçmak VH. Deneysel Diyabetin Serebellar CREB / BDNF Yolağı, Oksidatif Stres ve Motor Fonksiyona Etkisi. Turk J Diab Obes. 2021;5(3):248-55.

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