Volume 10, Issue 3 (Vol.10 No.3 Oct 2021)                   rbmb.net 2021, 10(3): 380-386 | Back to browse issues page

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Sahraiian V, Khazali H. Ghrelin Is Effective on Passive Avoidance Memory by Altering the Expression of NMDAR and HTR1a Genes in the Hippocampus of Male Wistar Rats. rbmb.net. 2021; 10 (3) :380-386
URL: http://rbmb.net/article-1-655-en.html
Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Abstract:   (266 Views)
Background: Memory-dependent psychological behaviors have an important role in life. Memory strengthening in adulthood to prevent its defects in aging is a significant issue. The ghrelin endogenous hormone improves memory by targeting glutamatergic and serotonergic circuits. Also, citicoline, a memory strengthening drug in aging, is not recommended to adults due to its side effects. The current study aims to test that ghrelin treatment, like citicoline, would improve passive avoidance memory via expression of the genes encoding the N-methyl-D-aspartate receptor (NMDAR1) and the serotonin receptor 1A (HTR1a) involved in this process.

Methods: Five groups of adult male rats received (1) saline (as control), (2) 0.5 mg/kg citicoline, or (3-5) 0.3, 1.5, and 3 nmol/μl ghrelin). The rats received the drugs via intra-hippocampal injection. Passive avoidance memory was determined using a shuttle box device. The latency to enter the dark chamber before (IL) and after (RL) injection and the total duration of the animal's presence in the light compartment (TLC) were evaluated. Then, the gene expression rates of NMDAR1 and HTR1a were measured by the Real-Time PCR. 

Results: Ghrelin and citicoline had some similar and significant effects on passive avoidance memory, and both increased NMDAR1 and decreased HTR1a expression. 

Conclusions: Ghrelin, like citicoline, improves passive avoidance learning by altering the NMDAR1 and HTR1a expression in the hippocampus.
Full-Text [PDF 298 kb]   (79 Downloads)    
Type of Article: Original Article | Subject: Molecular Biology
Received: 2021/02/10 | Accepted: 2021/04/18 | Published: 2021/12/5

References
1. Bayliss JA, Lemus MB, Stark R, Santos VV, Thompson A, Rees DJ, et al. Ghrelin-AMPK Signaling Mediates the Neuroprotective Effects of Calorie Restriction in Parkinson's Disease. J Neurosci. 2016;36(10):3049-63. [DOI:10.1523/JNEUROSCI.4373-15.2016] [PMID] [PMCID]
2. Lu YQ, Luo Y, He ZF, Chen J, Yan BL, Wang Y, et al. Hydroxysafflor yellow A ameliorates homocysteine-induced Alzheimer-like pathologic dysfunction and memory/synaptic disorder. Rejuvenation Res. 2013;16(6):446-52. [DOI:10.1089/rej.2013.1451] [PMID]
3. Hansson C, Haage D, Taube M, Egecioglu E, Salomé N, Dickson SL. Central administration of ghrelin alters emotional responses in rats: behavioural, electrophysiological and molecular evidence. Neuroscience. 2011;180:201-11. [DOI:10.1016/j.neuroscience.2011.02.002] [PMID]
4. Morin V, Hozer F, Costemale-Lacoste JF. The effects of ghrelin on sleep, appetite, and memory, and its possible role in depression: A review of the literature. Encephale. 2018;44(3):256-263. [DOI:10.1016/j.encep.2017.10.012] [PMID]
5. Mahmoudi F, Mohsennezhad F, Khazali H, Ehtesham H. The effect of central injection of ghrelin and bombesin on mean plasma thyroid hormones concentration. Iran J Pharm Res. 2011;10(3):627-32.
6. Matyja E, Taraszewska A, Nagańska E, Grieb P, Rafałowska J. CDP-choline protects motor neurons against apoptotic changes in a model of chronic glutamate excitotoxicity in vitro. Folia Neuropathol. 2008;46(2):139-48.
7. Petkov VD, Mosharrof AH, Kehayov R, Petkov VV, Konstantinova E, Getova D. Effect of CDP-choline on learning and memory processes in rodents. Methods Find Exp Clin Pharmacol. 1992;14(8):593-605.
8. Teather LA, Wurtman RJ. Dietary CDP-choline supplementation prevents memory impairment caused by impoverished environmental conditions in rats. Learn Mem. 2005;12(1):39-43. [DOI:10.1101/lm.83905] [PMID] [PMCID]
9. Li F, Tsien JZ. Memory and the NMDA receptors. N Engl J Med. 2009;361(3):302-303. [DOI:10.1056/NEJMcibr0902052] [PMID] [PMCID]
10. Ogundele OM, Nanakumo ET, Ishola AO, Obende OM, Enye LA, Balogun WG, et al. -NMDA R/+VDR pharmacological phenotype as a novel therapeutic target in relieving motor-cognitive impairments in Parkinsonism. Drug Chem Toxicol. 2015;38(4):415-27. [DOI:10.3109/01480545.2014.975355] [PMID]
11. Albert PR, Fiori LM. Transcriptional dys-regulation in anxiety and major depression: 5-HT1A gene promoter architecture as a therapeutic opportunity. Curr Pharm Des. 2014;20(23):3738-50. [DOI:10.2174/13816128113196660740] [PMID]
12. Akbari-Fakhrabadi M, Najafi M, Mortazavian S, Memari A-H, Shidfar F, Shahbazi A, et al. Saffron (Crocus Sativus L.), Combined with Endurance Exercise, Synergistically Enhances BDNF, Serotonin, and NT-3 in Wistar Rats. Rep Biochem Mol Biol. 2021;9(4):426-434. [DOI:10.52547/rbmb.9.4.426] [PMID] [PMCID]
13. Carlini VP, Monzón ME, Varas MM, Cragnolini AB, Schiöth HB, Scimonelli TN, et al. Ghrelin increases anxiety-like behavior and memory retention in rats. Biochem Biophys Res Commun. 2002;299(5):739-43. [DOI:10.1016/S0006-291X(02)02740-7]
14. Xu F, Hongbin H, Yan J, Chen H, He Q, Xu W, et al. Greatly improved neuroprotective efficiency of citicoline by stereotactic delivery in treatment of ischemic injury. Drug Deliv. 2011;18(7):461-7. [DOI:10.3109/10717544.2011.589084] [PMID]
15. Carlini VP, Varas MM, Cragnolini AB, Schiöth HB, Scimonelli TN, de Barioglio SR. Differential role of the hippocampus, amygdala, and dorsal raphe nucleus in regulating feeding, memory, and anxiety-like behavioral responses to ghrelin. Biochem Biophys Res Commun. 2004;313(3):635-41. [DOI:10.1016/j.bbrc.2003.11.150] [PMID]
16. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 2013.
17. Babri S, Badie HG, Khamenei S, Seyedlar MO. Intrahippocampal insulin improves memory in a passive-avoidance task in male wistar rats. Brain Cogn. 2007;64(1):86-91. [DOI:10.1016/j.bandc.2007.01.002] [PMID]
18. Bavarsad K, Hadjzadeh MA, Hosseini M, Pakdel R, Beheshti F, Bafadam S, et al. Effects of levothyroxine on learning and memory deficits in a rat model of Alzheimer's disease: the role of BDNF and oxidative stress. Drug Chem Toxicol. 2020;43(1):57-63. [DOI:10.1080/01480545.2018.1481085] [PMID]
19. Lohman RJ, Liu L, Morris M, O'Brien TJ. Validation of a method for localised microinjection of drugs into thalamic subregions in rats for epilepsy pharmacological studies. J Neurosci Methods. 2005;146(2):191-7. [DOI:10.1016/j.jneumeth.2005.02.008] [PMID]
20. Rezayof A, Habibi P, Zarrindast MR. Involvement of dopaminergic and glutamatergic systems of the basolateral amygdala in amnesia induced by the stimulation of dorsal hippocampal cannabinoid receptors. Neuroscience. 2011;175:118-26. [DOI:10.1016/j.neuroscience.2010.12.006] [PMID]
21. Bustin SA. Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol. 2000;25(2):169-93. [DOI:10.1677/jme.0.0250169] [PMID]
22. Mo Y, Wan R, Zhang Q. Application of reverse transcription-PCR and real-time PCR in nanotoxicity research. Methods Mol Biol. 2012;926:99-112. [DOI:10.1007/978-1-62703-002-1_7] [PMID] [PMCID]
23. Muniz BG, Isokawa M. Ghrelin receptor activity amplifies hippocampal N-methyl-d-aspartate receptor-mediated postsynaptic currents and increases phosphorylation of the GluN1 subunit at Ser896 and Ser897. Eur J Neurosci. 2015;42(12):3045-53. [DOI:10.1111/ejn.13107] [PMID] [PMCID]
24. Berrout L, Isokawa M. Ghrelin upregulates the phosphorylation of the GluN2B subunit of the NMDA receptor by activating GHSR1a and Fyn in the rat hippocampus. Brain Res. 2018;1678:20-26. [DOI:10.1016/j.brainres.2017.09.028] [PMID] [PMCID]
25. Secades JJ. Citicoline: pharmacological and clinical review, 2010 update. Rev Neurol. 2011;52 Suppl 2:S1-S62.
26. Danysz W, Parsons CG. Alzheimer's disease, β-amyloid, glutamate, NMDA receptors and memantine--searching for the connections. Br J Pharmacol. 2012;167(2):324-52. [DOI:10.1111/j.1476-5381.2012.02057.x] [PMID] [PMCID]
27. Ogren SO, Eriksson TM, Elvander-Tottie E, D'Addario C, Ekström JC, Svenningsson P, et al. The role of 5-HT(1A) receptors in learning and memory. Behav Brain Res. 2008;195(1):54-77. [DOI:10.1016/j.bbr.2008.02.023] [PMID]
28. Pitsikas N, Tsitsirigou S, Zisopoulou S, Sakellaridis N. The 5-HT1A receptor and recognition memory. Possible modulation of its behavioral effects by the nitrergic system. Behav Brain Res. 2005;159(2):287-93. [DOI:10.1016/j.bbr.2004.11.007] [PMID]
29. Persson J, Herlitz A, Engman J, Morell A, Sjölie D, Wikström J, et al. Remembering our origin: gender differences in spatial memory are reflected in gender differences in hippocampal lateralization. Behav Brain Res. 2013;256:219-28. [DOI:10.1016/j.bbr.2013.07.050] [PMID]
30. Frings L, Wagner K, Unterrainer J, Spreer J, Halsband U, Schulze-Bonhage A. Gender-related differences in lateralization of hippocampal activation and cognitive strategy. Neuroreport. 2006;17(4):417-21. [DOI:10.1097/01.wnr.0000203623.02082.e3] [PMID]

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