Investigating the effect of agmatine on cognitive functions

Year 2011, Volume: 1 Issue: 1, 8 - 16, 31.01.2014

Nimet Bozkurt Tijen Utkan Feyza Arıcıoğlu

Abstract

Objective: Learning and memory disorders are associated primary or secondary with many disease which affect the quality of life negatively. In this study, possible effect of agmatine on cognitive functions have been investigated.
Methods: Agmatine was applied after the disruption of cognitive functions by using amnesia or stress models in Wistar Albino rats. Muscarinic cholinergic receptor blocker scopolamine was used to create amnesia. In this model rats have been divided into 3 groups as control, scopolamine and scopolamine+agmatine. Control group has received saline, scopolamine group 1 mg/kg scopolamine, scopolamine+agmatine group 1mg/kg skopolamine and 20 min later 40 mg/kg agmatine intraperitoneally (i.p.). Animals were exposed to immobilization in order to create stress for 14 days, 4 hours per day. In this model, rats were divided into three groups as control, stress and stress+agmatine. After stress exposure saline was administered to control and stress groups and 40 mg/kg agmatine to stress+agmatine group. Animals were taken to Morris water maze and passive avoidance tests to evaluate learning and memory functions 30 min after the last injections.
Results: In our study, it has been shown that agmatine treatment significantly improved learning and memory impairment induced by both scopolamine or stress.
Conclusion: Based on these findings, it is thought that agmatine may have a positive effect on learning and memory functions, and also may play an important role in regulation of cognitive functions as an endogenous substance.

Key words: Agmatine, amnesia, memory, learning, scopolamine

Keywords

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Agmatinin Kognitif Fonksiyonlara Etkisinin Araştırılması

Abstract

Amaç: Öğrenme ve bellek bozuklukları; yaşam kalitesini olumsuz yönde etkileyen birçok hastalıkla primer veya sekonder olarak ilişkilidir. Bu çalışmada; agmatinin kognitif fonksiyonlar üzerine olası etkisi araştırılmıştır.
Yöntem: Sıçanlarda amnezi ve stres modelleri kullanılarak kognitif fonksiyonların bozulması sağlandıktan sonra agmatin uygulanmıştır. Amnezi oluşturmak için kolinerjik muskarinik reseptör blokeri skopolamin kullanılmış, hayvanlar kontrol, skopolamin ve skopolamin+agmatin olmak üzere üç gruba ayrılmıştır. Kontrol grubuna, serum fizyolojik, skopolamin grubuna 1 mg/kg skopolamin, skopolamin+agmatin grubuna 1 mg/kg skopolamin ve 20 dk sonra 40 mg/kg agmatin ntraperitoneal (i.p.) olarak uygulanmıştır. Stres oluşturmak için ise hayvanlar 14 gün süreyle günde 4 saat immobilizasyona maruz bırakılmıştır. Bu modeldeki hayvanlar kontrol, stres ve stres+agmatin olmak üzere üç gruba ayrılmıştır. Stres uygulamasının ardından kontrol ve stres gruplarına, s.f., stres+agmatin grubuna ise 40 mg/kg agmatin uygulanmıştır. Hayvanlar, son enjeksiyondan 30 dk sonra öğrenme ve bellek fonksiyonları değerlendirilmek üzere Morris’in su tankı ve pasif sakınma testlerine alınmıştır.
Bulgular: Çalışmamızda agmatin tedavisinin hem skopolamin,
hem de stres ile bozulmuş kognitif fonksiyonlarda anlamlı bir
düzelme sağladığı gösterilmiştir.
Sonuç: Bu bulgulardan hareketle, agmatinin bozulmuş öğrenme ve bellek fonksiyonlarına olumlu katkılarının olabileceği ve ayrıca endojen bir madde olarak kognitif fonksiyonların düzenlenmesinde önemli rolü olabileceği düşünülmüştür.

Anahtar sözcükler: Agmatin, amnezi, bellek, öğrenme, skopolamin

Keywords

Agmatin, amnezi, bellek, öğrenme, skopolamin

References

• Okano H, Hirano T, Balaban E. Learning and memory. PNAS 2000; 97: 12403-12404.
• Dere E, Pause BM, Pietrowsky R. Emotion and episodic memory in neuropsychiatric disorders. Behav Brain Res. 2010; 215(2):162-171.
• Karabekiroğlu K, Gımzal A, Berkem M. Psikiyatrik bozukluklarda bellek sorunları. Anadolu Psikiyatr Derg. 2005; 6: 188-196.
• Korn H, Faber DS. Quantal analysis and synaptic efficacy in the CNS. Trends Neurosci. 1991; 14: 439-445.
• Burgess N, Maguire EA, O’Keefe J. The human hippocampus and spatial and episodic memory. Neuron 2002; 35: 625-641.
• Aggleton JP, Brown MW. Episodic memory, amnesia, and the hippocampal-anterior thalamic axis. Behav Brain Sci. 1999; 22: 471-489.
• Dickerson BC, Eichenbaum H. The episodic memory system: Neurocircuitry and disorders. Neuropsychopharmacol. 2010; 35: 86-104.
• Niewiadomska G, Baksalerska-Pazera M, Riedel G. The septo- hippocampal system, learning and recovery of function. Prog Neuro Psychoph. 2009; 33: 791-805.
• Reis DJ, Regunathan S. Is agmatine a novel neurotransmitter in brain? TIPS 2000; 21: 187-193.
• Arıcıoğlu F. Sinir sisteminin fonksiyonlarını modüle edebilen yeni bir madde: Agmatin. RCHP 2008; 3-4: 27-37.
• Arıcıoğlu F. Agmatinin nöropsikiyatrideki yeri ve önemi. RCHP 2009; 1-2: 7-21.
• Arıcıoğlu F, Means A, Regunathan S. Effects of agmatine on the development of morphine dependence in rats: Potential role of cAMP system. Eur J Pharmacol. 2004; 504: 191-197.
• Arıcıoğlu F, Paul IA, Regunathan S. Agmatine reduces only peripheral related behavioral signs, not the central signs of morphine withdrawal in nNOS deficient transgenic mice. Neurosci Lett. 2004; 354: 153-157.
• Arıcıoğlu-Kartal F, Regunathan S. Effect of chronic morphine treatment on the biosynthesis of agmatine in rat brain and other tissues. Life Sci. 2002; 71: 1695-1701.
• Arıcıoğlu F, Korcegez E, Bozkurt A, Ozyalcin S. Effect of agmatine on acute and mononeuropathic pain. Ann NY Acad Sci. 2003; 1009: 106- 115.
• Arıcıoğlu F, Regunathan S. Agmatine attenuates stress- and lipopolysaccharide-induced fever in rats. Physiol Behav. 2005; 85: 370-375.
• Arıcıoğlu F, Kan B, Yillar O, Korceez E, Berkman K. Effect of agmatine on electrically and chemically induced seizures in mice. Ann NY Acad Sci. 2003; 1009: 141-146.
• Arıcıoğlu F, Regunathan S, Piletz J. Is agmatine an endogenous factor against stress? Ann NY Acad Sci. 2003; 1009: 127-132.
• Arıcıoğlu F, Altunbaş H. Is agmatine an endogenous anxiolytic/ antidepressant agent? Ann NY Acad Sci. 2003; 1009: 136-140.
• 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): 146-153.
• Liu P, Collie ND, Chary S, Jing Y, Zhang HSpatial learning results in elevated agmatine levels in the rat brain. Hippocampus 2008; 18: 1094-1098.
• Zarifkar A, Choopani S, Ghasemi R, Naghdi N, Maghsoudi AH, Maghsoudi N, Rastegar K, Moosavi M. Agmatine prevents LPS- induced spatial memory impairment and hippocampal apoptosis. Eur J Pharmacol. 2010; 634: 84-88.
• Roozendaal B, McEwen BS, Chattarji S. Stress, memory and the amygdala. Nature Rev Neurosci. 2009; 10: 423-433.
• Song L, Che W, Min-wei A, Murakami Y, Matsumoto K. Impairment of the spatial learning and memory induced by learned helplessness and chronic mild stress. Pharmacol Biochem Behav. 2006; 83: 186-193.
• Morris, R. G. M. Spatial Localization Does Not Require the Presence of Local Cues. Learning and Motivation 1981; 12(2): 239-260.
• Kameyama T, Nabeshima T, Kozawa TStep-down-type passive avoidance- and escape-learning method. Suitability for experimental amnesia models. J Pharmacol Methods. . 1986; 16(1): 39-52.
• Stewart LS, McKay BE. Acquisition deficit and time-dependent retrograde amnesia for contextual fear conditioning in agmatine- treated rats. Behav Pharmacol. 2000; 11: 93-97.
• McKay BE, Lado WE, Martin LJ, Galic MA, Fournier NM. Learning and memory in agmatine-treated rats. Pharmacol Biochem Behav. 2002; 72: 551-557.
• Lu W, Dong HJ, Gong Z, Su RB, Li JAgmatine inhibits morphine- induced memory impairment in the mouse step-down inhibitory avoidance task. Pharmacol Biochem Behav. 2010; 97(2):256-261.
• 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: 465-469.
• Liu P, Bergin DH. Differential effects of i.c.v. microinfusion of agmatine on spatial working and reference memory in the rat. Neurosci. 2009; 159: 951-961.
• Liu P, Collie ND. Behavioral effects of agmatine in naive rats are task- and delay-dependent. Neurosci. 2009; 163: 82-96.
• Hasselmo ME. The role of acetylcholine in learning and memory. Curr Opin Neurobiol. 2006; 16: 710-715.
• Armstrong DM, Saper CB, Levey AI, Wainer BH, Te RD. Distribution of cholinergic neurons in rat brain: Demonstrated by the immunocytochemical localization of choline acetyltransferase. J Comp Neurol. 2004; 216: 53-68.
• Friedman A, Kaufer D, Pavlovsky L. Cholinergic excitation induces activity-dependent electrophysiological and transcriptional responses in hippocampal slices. J Physiol. 1998; 92: 329-335.
• Klinkenberg I, Blokland A. The validity of scopolamine as a pharmacological model for cognitive impairment: A review of animal behavioral studies. Neurosci Biobehav Rev. 2010; 34: 1307-1350.
• Eglen RM, Nahorski SR. The muscarinic M5 receptor: A silent or emerging subtype? Br J Pharmacol. 2000; 130: 13-21.
• Riedel G, Platt B, Micheaub J. Glutamate receptor function in learning and memory. Behav Brain Res. 2003; 140: 1-47.
• Myhrer T. Neurotransmitter systems involved in learning and memory in the rat: A meta-analysis based on studies of four behavioral tasks. Brain Res Rev. 2003; 41: 268-287.
• Wiley JL, Willmore CB. Effects of nitric oxide synthase inhibitors on timing and short-term memory in rats. Behav Pharmacol. 2000; 11: 421-429.
• Huang AM, Lee EH. Role of hippocampal nitric oxide in memory retention in rats. Pharmacol Biochem Behav. 1995; 50: 327-332.
• Bidmon HJ, Wu N, Palomero-Gallagher E, Oermann B, Mayer A, Schleicher A, Zilles K. Different nitric oxide synthase inhibitors cause rapid and differential alterations in the ligand-binding capacity of transmitter receptors in the rat cerebral cortex. Ann Anat. 1999; 181: 345-351.
• Paakkaria I, Lindsbergb P. Nitric oxide in the central nervous system. Ann Med. 1995; 27: 369-377.
• Stevanović ID, Jovanović MD, Ankica Jelenković MČ, Bokonjić D, Ninković M. Nitric oxide synthase inhibitors protect cholinergic neurons against AlCl3 excitotoxicity in the rat brain. Brain Res Bull. 2010; 81: 641-646.
• Susswein AJ, Katzoff A, Miller N and Hurwitz I. Nitric oxide and memory. Neuroscientist 2004; 10: 153-154.
• Radecki DT, Brown LM, Martinez J, Teyler TJ. BDNF protects against stress-induced impairments in spatial learning and memory and LTP. Hippocampus 2005; 15: 246-253.
• Lynch MA. Long-term potentiation and memory. Physiol Rev. 2004; 84: 87-136.
• Kaufer D, Friedman A, Seidman SAcute stress facilitates long-lasting changes in cholinergic gene expression. Nature 1998; 28: 373-377.
• Spedding M, Neau I, Harsing L. Brain plasticity and pathology in psychiatric disease: Sites of action for potential therapy. Curr Opin Pharmacol. 2003; 3: 33- 40.
• Pae C, Marks DM, Han C. Does neurotrophin -3 have a therapeutic implication in major depression? Int J Neurosci. 2008; 118: 1515– 1522.