YAŞLI SIÇANLARDA AGMATİN TAKVİYESİ VE AEROBİK EGZERSİZİN UZAYSAL ÖĞRENME ÜZERİNE ETKİSİ

Yıl 2021, Cilt: 22 Sayı: 2, 98 - 105, 12.04.2021

Mustafa Savaş Torlak , Nilsel Okudan , Muaz Belviranlı

https://doi.org/10.18229/kocatepetip.620688

Öz

AMAÇ: Çalışmanın amacı, yaşlı sıçanlarda agmatin takviyesi ve egzersizin kognitif fonksiyonlar üzerine etkilerinin incelenmesidir.
GEREÇ VE YÖNTEM: Çalışmada, 300-350 gr ağırlığında, 36 adet sağlıklı yaşlı erkek Sprague-Dawley sıçan kullanıldı. Sıçanlar rastgele olarak kontrol (n=6), egzersiz (n=10), agmatin (n=10), agmatin+egzersiz (n=10) gruplarına ayrıldı. Kontrol grubunda ve Egzersiz grubunda yer alan sıçanlara 8 hafta 1 mg/kg (i.p) serum fizyolojik uygulandı. Agmatin gruplarında bulunan sıçanlara 8 hafta 40 mg/kg (i.p) agmatin takviyesi uygulandı. Egzersiz ve agmatin+egzersiz gruplarına 8 hafta boyunca yüzme egzersizi uygulandı. 8. haftanın sonunda Morris su labirent testi gerçekleştirildi. Tüm hayvanlar dekapite edildi ve beyin kaynaklı nörotrofik faktör (plazmada), hipokampuste agmatin ve nitrit+nitrat seviyelerinin ölçümü için kan ve doku (hipokampus) örnekleri alındı. Protein konsantrasyonu Lowry metoduyla tayin edildi.
BULGULAR: Agmatin seviyesi agmatin ve agmatin+egzersiz gruplarında kontrol grubu ve egzersiz grubuna göre belirgin şekilde yüksekti (p<0.05). Beyin kaynaklı nörotrofik faktör (BDNF) seviyesi ve nitrit+nitrat seviyeleri bakımından gruplar arasında belirgin bir fark yoktu (p<0.05). Morris su labirent testi deneme fazında 1. gün ve 4. gün gruplar arasında toplam kat edilen mesafe ve platformu bulma süreleri açısından fark yoktu (p<0.05). 2. gün ve 3. gün toplam kat edilen mesafe ve platformu bulma süreleri kontrol grubuna göre agmatin+egzersiz grubunda daha düşüktü (p<0.05).
SONUÇ: Agmatin takviyesinin yaşlı sıçanlarda uzaysal öğrenme üzerine olumlu etkileri olabileceği gözlemlendi.

Anahtar Kelimeler

Agmatin, Beyin kaynaklı nörotrofik faktör,, Egzersiz, ,Öğrenme

Destekleyen Kurum

Selçuk Üniversitesi Bilimsel Araştırma Projeleri

Proje Numarası

14202030

EFFECTS OF AGMATINE SUPPLEMENTATION AND AEROBIC EXERCISE ON SPATIAL LEARNING IN AGED RATS

Öz

OBJECTIVE: The aim of the study is to examine the effects of agmatine supplementation and exercise on cognitive functions of aged rats.
MATERIAL AND METHODS: In the study, 36 healthy, old male Sprague-Dawley rats with a weight of 300-350 gr were used. The rats were randomly divided into as control (n=6), exercise (n=10), agmatine (n=10), agmatine+exercise (n=10) groups. The rats in the control group and the exercise group were administered 1 mg / kg (i.p) saline for 8 weeks. 40 mg/kg (i.p) Agmatine supplementation was given to the rats at the agmatine groups. Swimming exercise was applied for 8 weeks to the exercise and agmatine+exercise groups. At the end of the 8th week, Morris maze test was concluded. All the animals were decapitated and the blood and tissue samples (hippocampus) were taken for measuring brain derived neurotrophic factor (in plasma), the agmatine and nitrite+nitrate levels in hippocampus. Protein concentration was determined by the Lowry method.
RESULTS: Agmatine level was significantly higher in the agmatine and agmatine+exercise groups compared to the control group and exercise group (p<0.05). In terms of the brain derived neurotrophic factor (BDNF) and nitrite+nitrate levels there was no significant difference between the groups (p<0.05). On the first day and fourth day, there was no difference between the groups in terms of total logged distance and durations of finding the platform at the phase of Morris water maze test (p<0.05). On the second day and third day, the total logged distance and durations of finding the platform was lower in the agmatine+exercise group compared to the control group (p<0.05).
CONCLUSIONS: It was observed that agmatine supplementation might have positive effects on spatial learning in aged rats.

Anahtar Kelimeler

Agmatine,, Brain derived neurotrophic factor, Exercise, Learning

Proje Numarası

14202030

Kaynakça

• Cooke SF, Bliss TV. Plasticity in the human central nervous system. Brain 2006; 129(7):1659-73.
• Maren S, Baudry M. Properties and mechanisms of long-term synaptic plasticity in the mammalian brain: relationships to learning and memory. Neurobiol Learn Mem 1995; 63( 1):1-18.
• Ehninger D, Kempermann G. Neurogenesis in the adult hippocampus. Cell Tissue Res 2008; 331(1):243-50.
• Spalding KL, Bergmann O, Alkass K, et al. Dynamics of hippocampal neurogenesis in adult humans. Cell 2013;153 (6):1219-27.
• Bruel-Jungerman E, Rampon C, Laroche S. Adult hippocampal neurogenesis, synaptic plasticity and memory: facts and hypotheses. Rev Neurosci 2007;18(2):93-114.
• Winocur G, Wojtowicz JM, Sekeres M, Snyder JS, Wang S. Inhibition of neurogenesis interferes with hippocampus-dependent memory function. Hippocampus 2006; 16(3):296-304.
• Jessberger S, Clark RE, Broadbent NJ, et al. Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats. Learn Mem 2009;16(2):147-54.
• Lewin G, Carter BD. Neurotrophic factors. Newyork, Springer 2014:3-13.
• Ahlskog JE, Geda YE, Graff-Radford NR, Petersen RC. Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clin Proc 2011; 86(9):876-84.
• Kronenberg G, Bick-Sander A, Bunk E, Wolf C, Ehninger D, Kempermann G. Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus. Neurobiol Aging 2006; 27(10):1505-13.
• O'Callaghan RM, Griffin EW, Kelly AM. Long-term treadmill exposure protects against age-related neurodegenerative change in the rat hippocampus. Hippocampus 2009; 19(10):1019-29.
• Uzbay TI. The pharmacological importance of agmatine in the brain. Neurosci Biobehav Rev 2012; 36(1):502-19.
• Moinard C, Cynober L, de Bandt JP. Polyamines: metabolism and implications in human diseases. Clin Nutr 2005; 24(2):184-97.
• Taksande BG, Kotagale NR, Patel MR, Shelkar GP, Ugale RR, Chopde CT. Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats. Eur J Pharmacol 2010; 637(1-3):89-101.
• Molderings GJ, Haenisch B. Agmatine (decarboxylated L-arginine): physiological role and therapeutic potential. Pharmacol Ther 2012;133(3):351-65.
• Mun CH, Lee WT, Park KA, Lee JE. Regulation of endothelial nitric oxide synthase by agmatine after transient global cerebral ischemia in rat brain. Anat Cell Biol 2010; 43(3):230-40.
• 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):1094-8.
• Leitch B, Shevtsova O, Reusch K, Bergin DH, Liu P. Spatial learning-induced increase in agmatine levels at hippocampal CA1 synapses. Synapse 2011; 65(2):146-53.
• Rushaidhi M, Collie ND, Zhang H, Liu P. Agmatine selectively improves behavioural function in aged male Sprague-Dawley rats. Neuroscience 2012; 218: 206-15.
• Rushaidhi M, Jing Y, Zhang H, Liu P. Participation of hippocampal agmatine in spatial learning: an in vivo microdialysis study. Neuropharmacology 2013; 65: 200-5.
• Liu P, Jing Y, Collie ND, Chary S, Zhang H. Memory-related changes in L-citrulline and agmatine in the rat brain. Hippocampus 2009; 19(7):597-602.
• Seo S, Liu P, Leitch B. Spatial learning-induced accumulation of agmatine and glutamate at hippocampal CA1 synaptic terminals. Neuroscience 2011;192: 28-36.
• Campos-Ferraz PL, Bozza T, Nicastro H, Lancha AH. Distinct effects of leucine or a mixture of the branched chain amino acids (leucine, isoleucine and valine) supplementation on resistance to fatigue and muscle and liver glycogen degration in trained rats. Nutrition 2013; 29: 1388-1394.
• Okudan N, Belviranli M. Long-term voluntary exercise prevents post-weaning social isolation-induced cognitive impairment in rats. Neuroscience 2017; 360: 1-8.
• Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193: 265-75.
• Wang S, Chen L, Zhang L, Huang C, Xiu Y, Wang F. Effects of long term exercise on spatial learning, memory ability and cortical capillaries in aged rats. Med Sci Monit 2015; 21:945-54.
• Voss MW, Prakash RS, Erickson KI, et al. Plasticityof brain networks in a randomized intervention trial of exercise training in older adults. Front Aging Neurosci 2010; 26(32):1-17.
• Cetinkaya C, Sisman AR, Kiray M, et al. Positive effects of aerobic exercise on learning and memory functioning, which correlate with hippocampal IGF-1 increase in adolescent rats. Neurosci Lett 2013; 549: 177-81.
• Creer DJ, Romberg C, Saksida LM, van Praag H, Bussey TJ. Running enhances spatial pattern separation in mice. Proc Natl Acad Sci USA 2010; 107(5):2367-72.
• Asl NA, Sheikhzade F, Torchi M, Roshangar L, Khamnei S. Long-term regular exercise promotes memory and learning in young but not in older rats. Pathophysiology 2008; 15(1):9-12.
• Brunelli A, Dimauro I, Sgro P, et al. Acute exercise modulates BDNF and pro-BDNF protein content in immune cells. Med Sci Sports Exerc 2012; 44(10):1871-80.
• Seifert T, Brassard P, Wissenberg M, et al. Endurance training enhances BDNF release from the human brain. Am J Physiol Regul Integr Comp Physiol 2010; 298(2):372-7.
• Correia PR, Pansani A, Machado F, et al. Acute strength exercise and the involvement of small or large muscle mass on plasma brain-derived neurotrophic factor levels. Clinics 2010; 65(11):1123-6.
• Sılhol M, Arancibia S, Maurice T, Tapia-Arancibia L. Spatial memory training modifies the expression of brain derived neurotrophic factor tyrosine kinase receptors in young and aged rats. Neuroscience 2007;146: 962-73.
• Adlard PA, Perreau VM, Cotman CW. The exercise-induced expression of BDNF within the hippocampus varies across life-span. Neurobiol Aging 2005; 26: 511-20.
• 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):951-61.
• Liu P, Collie ND. Behavioral effects of agmatine in naive rats are task- and delay-dependent. Neuroscience 2009; 163(1):82-96.
• Ahn SK, Hong S, Park YM, Lee WT, Park KA, Lee JE. Effects of agmatine on hypoxic microglia and activity of nitric oxide synthase. Brain Res 2011;1373: 48-54.
• Cui H, Lee JH, Kim JY, Koo BN, Lee JE. The neuroprotective effect of agmatine after focal cerebral ischemia in diabetic rats. J Neurosurg Anesthesiol 2012; 24(1):39-50.
• Demady DR, Jianmongkol S, Vuletich JL, Bender AT, Osawa Y. Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme. Mol Pharmacol 2001;59(1):24-9.
• Raghavan SA, Dikshit M. Vascular regulation by the L-arginine metabolites, nitric oxide and agmatine. Pharmacol Res 2004;49(5):397-414.