Sinan SARAL, Ali Koray KAYA, Atilla TOPÇU, Aykut ÖZTÜRK, Ayşegül SÜMER, Esra PINARBAŞ

Agomelatin Yetişkin Sıçanlarda Skopolamin Kaynaklı Öğrenme ve Hafıza Bozukluğunu Tersine Çevirir

Amaç: Agomelatin, melatonin reseptör (MT1 ve MT2) agonisti ve serotonin reseptör (5-HT2C) antagonisti olan antidepresan bir ilaçtır. Artan kanıtlar, agomelatinin nöroprotektif ve nöromodülatör etkiye sahip olduğunu göstermektedir. Bu çalışmada skopolamin indüklü bilişsel yetmezlik oluşturulan sıçanlarda agomelatinin potansiyel etkileri araştırılmıştır.

Anahtar Kelimeler:

Agomelatin, asetilkolin, BDNF, bellek, bilişsel yetmezlik

Agomelatine Reverses Scopolamine-Induced Learning and Memory Impairment in Adult Rats

Objective: The antidepressant agomelatine agent is a melatonin receptor (MT1 and MT2) agonist and a serotonin receptor (5-HT2C) antagonist. Increasing evidence shows that agomelatine has neuroprotective and neuromodulatory effects. In this study, the potential effects of agomelatine in rats with scopolamine-induced cognitive impairment were investigated.

Keywords:

Cognitive impairment, agomelatine, spatial memory, BDNF, acetylcholine,

PDF

___

Deture MA, Dickson DW. The neuropathological diagnosis of Alzheimer ’ s disease. 2019;5:1-18.
Grimm A, Mensah-Nyagan AG, Eckert A. Alzheimer, mitochondria and gender. Neurosci Biobehav Rev. 2016;67:89-101. doi:10.1016/j.neubiorev.2016.04.012
Dos Santos TC, Gomes TM, Pinto BAS, Camara AL, De Andrade Paes AM. Naturally occurring acetylcholinesterase inhibitors and their potential use for Alzheimer’s disease therapy. Front Pharmacol. 2018;9(OCT):1-14. doi:10.3389/fphar.2018.01192
Craig LA, Hong NS, McDonald RJ. Revisiting the cholinergic hypothesis in the development of Alzheimer’s disease. Neurosci Biobehav Rev. 2011;35(6):1397-1409. doi:10.1016/j.neubiorev.2011.03.001
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(8):1307-1350. doi:10.1016/j.neubiorev.2010.04.001
Haider S, Tabassum S, Perveen T. Scopolamine-induced greater alterations in neurochemical profile and increased oxidative stress demonstrated a better model of dementia: A comparative study. Brain Res Bull. 2016;127:234-247. doi:10.1016/j.brainresbull.2016.10.002
Tota SK, Hanif K, Kamat PK, Najmi AK, Nath C. Role of central angiotensin receptors in scopolamine-induced impairment in memory, cerebral blood flow, and cholinergic function. Psychopharmacology (Berl). 2012;222(2):185-202. doi:10.1007/s00213-012-2639-7
Lu C, Wang Y, Xu T, et al. Genistein ameliorates scopolamine-induced amnesia in mice through the regulation of the cholinergic neurotransmission, antioxidant system and the ERK/CREB/BDNF signaling. Front Pharmacol. 2018;9(OCT):1-11. doi:10.3389/fphar.2018.01153
Chen BH, Park JH, Lee TK, et al. Melatonin attenuates scopolamine-induced cognitive impairment via protecting against demyelination through BDNF-TrkB signaling in the mouse dentate gyrus. Chem Biol Interact. 2018;285(January):8-13. doi:10.1016/j.cbi.2018.02.023
Papp M, Gruca P, Boyer PA, Mocaer E. Effect of agomelatine in the chronic mild stress model of depression in the rat. Neuropsychopharmacology. 2003;28(4):694-703. doi:10.1038/sj.npp.1300091
Rainer Q, Xia L, Guilloux JP, et al. Beneficial behavioural and neurogenic effects of agomelatine in a model of depression/anxiety. Int J Neuropsychopharmacol. 2012;15(3):321-335. doi:10.1017/S1461145711000356
Can ÖD, Üçel Uİ, Özkay ÜD, Ulupınar E. The effect of agomelatine treatment on diabetes-induced cognitive impairments in rats: Concomitant alterations in the hippocampal neuron numbers. Int J Mol Sci. Published online 2018. doi:10.3390/ijms19082461
Molteni R, Calabrese F, Pisoni S, et al. Synergistic mechanisms in the modulation of the neurotrophin BDNF in the rat prefrontal cortex following acute agomelatine administration. World J Biol Psychiatry. 2010;11(2):148-153. doi:10.3109/15622970903447659
Gumuslu E, Mutlu O, Sunnetci D, et al. The antidepressant agomelatine improves memory deterioration and upregulates CREB and BDNF gene expression levels in unpredictable chronic mild stress (UCMS)-exposed mice. Drug Target Insights. 2014;2014(8):11-21. doi:10.4137/DTI.S13870
Martin V, Allaïli N, Euvrard M, et al. Effect of agomelatine on memory deficits and hippocampal gene expression induced by chronic social defeat stress in mice. Sci Rep. 2017;8(March):1-11. doi:10.1038/srep45907
Gupta S, Singh P, Sharma B, Sharma B. Neuroprotective Effects of Agomelatine and Vinpocetine Against Chronic Cerebral Hypoperfusion Induced Vascular Dementia. Curr Neurovasc Res. 2015;12(3):240-252. doi:10.2174/1567202612666150603130235
Özkay ÜD, Söztutar E, Can ÖD, Üçel UI, Öztürk Y, Ulupinar E. Effects of long-term agomelatine treatment on the cognitive performance and hippocampal plasticity of adult rats. Behav Pharmacol. Published online 2015. doi:10.1097/FBP.0000000000000153
Ennaceur A, Delacour J. A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data. Behav Brain Res. Published online 1988. doi:10.1016/0166-4328(88)90157-X
Tian SW, Xu F, Gui SJ. Apelin-13 reverses memory impairment and depression-like behavior in chronic social defeat stressed rats. Peptides. Published online 2018. doi:10.1016/j.peptides.2018.08.009
Saral S, Topçu A, Alkanat M, et al. Apelin-13 activates the hippocampal BDNF/TrkB signaling pathway and suppresses neuroinflammation in male rats with cisplatin-induced cognitive dysfunction. Behav Brain Res. 2021;408:113290. doi:10.1016/j.bbr.2021.113290
Jafarian S, Ling KH, Hassan Z, Perimal-Lewis L, Sulaiman MR, Perimal EK. Effect of zerumbone on scopolamine-induced memory impairment and anxiety-like behaviours in rats. Alzheimer’s Dement Transl Res Clin Interv. 2019;5:637-643. doi:10.1016/j.trci.2019.09.009
Janas AM, Cunningham SC, Duffy KB, et al. The cholinesterase inhibitor, phenserine, improves Morris water maze performance of scopolamine-treated rats. Life Sci. 2005;76(10):1073-1081. doi:10.1016/j.lfs.2004.06.028
Lee JC, Park JH, Ahn JH, et al. Effects of chronic scopolamine treatment on cognitive impairment and neurofilament expression in the mouse hippocampus. Mol Med Rep. 2018;17(1):1625-1632. doi:10.3892/mmr.2017.8082
Kim DH, Ryu JH. Differential effects of scopolamine on memory processes in the object recognition test and the Morris water maze test in mice. Biomol Ther. 2008;16(3):173-178. doi:10.4062/biomolther.2008.16.3.173
Ko YH, Kwon SH, Lee SY, Jang CG. Isoorientin improves scopolamine-induced cognitive impairments by restoring the cholinergic system, antioxidant defense, and p-CREB/BDNF signaling in the hippocampus and frontal cortex. Arch Pharm Res. 2019;42(8):722-731. doi:10.1007/s12272-019-01172-7
Gumuslu E, Mutlu O, Sunnetci D, et al. The antidepressant agomelatine improves memory deterioration and upregulates CREB and BDNF gene expression levels in unpredictable chronic mild stress (UCMS)-exposed mice. Drug Target Insights. 2014;2014(8):11-21. doi:10.4137/DTI.S13870
Lu Y, Ho CS, McIntyre RS, Wang W, Ho RC. Agomelatine-induced modulation of brain-derived neurotrophic factor (BDNF) in the rat hippocampus. Life Sci. 2018;210(August):177-184. doi:10.1016/j.lfs.2018.09.003
Lee B, Shim I, Lee H, Hahm DH. Rehmannia glutinosa ameliorates scopolamine-induced learning and memory impairment in rats. J Microbiol Biotechnol. 2011;21(8):874-883. doi:10.4014/jmb.1104.04012
Klaassens BL, van Gerven JMA, Klaassen ES, van der Grond J, Rombouts SARB. Cholinergic and serotonergic modulation of resting state functional brain connectivity in Alzheimer’s disease. Neuroimage. 2019;199(October 2018):143-152. doi:10.1016/j.neuroimage.2019.05.044
Wong-Guerra M, Jiménez-Martin J, Fonseca-Fonseca LA, et al. JM-20 protects memory acquisition and consolidation on scopolamine model of cognitive impairment. Neurol Res. 2019;41(5):385-398. doi:10.1080/01616412.2019.1573285