The Protective Effect of Agmatine Against Intracerebroventricular Streptozotocin-Induced Memory Impairment in Male Rats
DOI:
https://doi.org/10.22100/jkh.v9i3.270Keywords:
Streptozotocin, Agmatine, Learning, Memory, Morris water maze, RatAbstract
Introduction: Intracerebroventricular injection of streptozotocin leads to learning and memory impairment. Different mechanisms such as oxidative stress and insulin signaling disruption has been proposed for streptozocin induced learning and memory deterioration. As these changes occur in Alzheimer's disease, this model is widely used to assess Alzheimer's disease. Agmatine is a polyamine derived from L-arginine decarboxylation. Agmatine is shown to have various effects such as neuroprotective role. Therefore, the present study was aimed to assess the plausible protective effect of agmatine against streptozocin induced memory impairment.
Methods: Male sprague-dawely rats weighing 200-250 g were used in this study. Within surgery the canules were implanted bilaterally into lateral ventricle. Streptozocin was injected on days 1 and 3 (3 mg/kg in divided doses). Agmatine administration (40 and 80 mg/kg) was started from day 4 and continued in an alternate manner till day 14. The animal’s learning and memory capability was assessed on days 15-18 using morris water maze. The animals were trained during 3 days, and on day 4, the probe test was done. In order to assess the effect of drugs on motivation and sensorimotor coordination, a visible platform test was performed after the probe trial.
Results: While streptozocin injection led to learning and memory disability, agmatine treatment in dose 80 mg/kg but not 40 mg/kg restored this memory impairment.
Conclusion: It seems that agmatine might be beneficial for memory impairment caused by Alzheimer’s disease.
References
Salkovic-Petrisic M, Knezovic A, Hoyer S, Riederer P. What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer's disease, about the therapeutic strategies in Alzheimer's research. Journal of Neural Transmission 2013;120(1):52-233.
Mayer G, Nitsch R, Hoyer S. Effects of changes in peripheral and cerebral glucose metabolism on locomotor activity, learning and memory in adult male rats. Brain Research 1990;532(1-2):95-100.
Blondel O, Portha B. Early appearance of in vivo insulin resistance in adult streptozotocin-injected rats. Diabete & Metabolisme 1989;15(6):382-7.
Lackovic Z, Salkovic M. Streptozotocin and alloxan produce alterations in rat brain monoamines independently of pancreatic beta cells destruction. Life Sciences 1990;46(1):49-54.
Shingo AS, Kanabayashi T, Kito S, Murase T. Intracerebroventricular administration of an insulin analogue recovers STZ-induced cognitive decline in rats. Behavioural Brain Research 2013;241:105-11.
Chueh W-H, Lin J-Y. Berberine, an isoquinoline alkaloid, inhibits streptozotocin-induced apoptosis in mouse pancreatic islets through down-regulating Bax/Bcl-2 gene expression ratio. Food Chemistry 2012;132(1):252-60.
Tabor CW, Tabor H. Polyamines. Annual Review of Biochemistry 1984;53:749-90.
Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJ. Agmatine: an endogenous clonidine-displacing substance in the brain. Science (New York, NY) 1994;263(5149):966-9.
Raasch W, Regunathan S, Li G, Reis DJ. Agmatine, the bacterial amine, is widely distributed in mammalian tissues. Life Sciences 1995;56(26):2319-30.
Halaris A, Plietz J. Agmatine : metabolic pathway and spectrum of activity in brain. CNS Drugs 2007;21(11):885-90.
Gilad GM, Gilad VH, Finberg JP, Rabey JM. Neurochemical evidence for agmatine modulation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity. Neurochemical Research 2005;30(6-7):713-9.
Gilad GM, Gilad VH. Accelerated functional recovery and neuroprotection by agmatine after spinal cord ischemia in rats. Neuroscience Letters 2000;296(2-3):97-100.
Moosavi M, Khales GY, Abbasi L, Zarifkar A, Rastegar K. Agmatine protects against scopolamine-induced water maze performance impairment and hippocampal ERK and Akt inactivation. Neuropharmacology 2012;62(5-6):2018-23.
Zarifkar A, Choopani S, Ghasemi R, Naghdi N, Maghsoudi AH, Maghsoudi N, et al. Agmatine prevents LPS-induced spatial memory impairment and hippocampal apoptosis. European journal of Pharmacology 2010;634(1-3):84-8.
Piletz JE, May PJ, Wang G, Zhu H. Agmatine crosses the blood-brain barrier. Annals of the New York Academy of Sciences 2003;1009:64-74.
Bolzan AD, Bianchi MS. Chromosomal response of human lymphocytes to streptozotocin. Mutation Research 2002;503(1-2):63-8.
Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiological Research/ Academia Scientiarum Bohemoslovaca 2001;50(6):537-46.
Agrawal R, Tyagi E, Shukla R, Nath C. Insulin receptor signaling in rat hippocampus: a study in STZ (ICV) induced memory deficit model. Eur Neuropsychopharmacol 2011;21(3):261-73.
Hong S, Lee JE, Kim CY, Seong GJ. Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line. BMC Neuroscience 2007;8:81.
Shingo AS, Kanabayashi T, Murase T, Kito S. Cognitive decline in STZ-3V rats is largely due to dysfunctional insulin signalling through the dentate gyrus. Behavioural Brain Research 2012;229(2):378-83.
Annunziato L, Amoroso S, Pannaccione A, Cataldi M, Pignataro G, D'Alessio A, et al. Apoptosis induced in neuronal cells by oxidative stress: role played by caspases and intracellular calcium ions. Toxicology Letters 2003;139(2-3):125-33.
Battaglia V, Grancara S, Satriano J, Saccoccio S, Agostinelli E, Toninello A. Agmatine prevents the Ca(2+)-dependent induction of permeability transition in rat brain mitochondria. Amino Acids 2010;38(2):431-7.
Condello S, Curro M, Ferlazzo N, Caccamo D, Satriano J, Ientile R. Agmatine effects on mitochondrial membrane potential andNF-kappaB activation protect against rotenone-induced cell damage in human neuronal-like SH-SY5Y cells. Journal of Neurochemistry 2011;116(1):67-75.
van Houten M, Posner BI, Kopriwa BM, Brawer JR. Insulin-binding sites in the rat brain: in vivo localization to the circumventricular organs by quantitative radioautography. Endocrinology 1979;105(3):666-73.
Hill JM, Lesniak MA, Pert CB, Roth J. Autoradiographic localization of insulin receptors in rat brain: prominence in olfactory and limbic areas. Neuroscience 1986;17(4):1127-38.
Devaskar SU, Giddings SJ, Rajakumar PA, Carnaghi LR, Menon RK, Zahm DS. Insulin gene expression and insulin synthesis in mammalian neuronal cells. The Journal of Biological Chemistry 1994;269(11):8445-54.
Santos MS, Pereira EM, Carvaho AP. Stimulation of immunoreactive insulin release by glucose in rat brain synaptosomes. Neurochemical Research 1999;24(1):33-6.
Nitsch R, Hoyer S. Local action of the diabetogenic drug, streptozotocin, on glucose and energy metabolism in rat brain cortex. Neuroscience Letters 1991;128(2):199-202.
Hawkins BT, Ocheltree SM, Norwood KM, Egleton RD. Decreased blood-brain barrier permeability to fluorescein in streptozotocin-treated rats. Neuroscience Letters 2007;411(1):1-5.
Wu N, Su RB, Li J. Agmatine and imidazoline receptors: their role in opioid analgesia, tolerance and dependence. Cellular and Molecular Neurobiology 2008;28(5):629-41.
Su CH, Liu IM, Chung HH, Cheng JT. Activation of I2-imidazoline receptors by agmatine improved insulin sensitivity through two mechanisms in type-2 diabetic rats. Neuroscience letters 2009;457(3):125-8.
Gerozissis K. Brain insulin: regulation, mechanisms of action and functions. Cellular and Molecular Neurobiology 2003;23(1):1-25.
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