Monosodyum Glutamatın Normal Sıçan Yaşlanmasında Korteks ve Hipokampüs Üzerine Etkilerinin Araştırılması

Year 2026, Volume: 10 Issue: 1, 69 - 82, 31.01.2026

Gürkan Baytar , Aslı Okan Oflamaz , Züleyha Doğanyiğit , Tuncer Kutlu , Arda Uner , Enes Akyüz , Hikmet Baytar , Serdal Öğüt

https://doi.org/10.46237/amusbfd.1666499

Abstract

Amaç: Bu araştırma, Monosodyum Glutamat (MSG) uygulanan yaşlı sıçanların korteks ve hipokampüs dokularında dopamin taşıyıcısı (DAT), dopamin reseptörü 1 (D1) ve D2 ekspresyonlarını araştırmak amacıyla yapılmıştır.
Yöntem: Deney gruplarının beyin dokularında hipokampüs ve korteksteki nöronal dejenerasyon ve genişlemiş kan damarları histopatolojik analizle değerlendirildi. DAT, D1 ve D2'nin immünoreaktivitesi immünohistokimyasal analizle belirlendi.
Bulgular: Korteksteki nöronal dejenerasyon yaşlı sıçanlarda kontrol grubuna kıyasla anlamlı derecede daha yüksekti. Yaşlı sıçanların hipokampüsünde ve korteksinde DAT, D1 ve D2 reaktiviteleri kontrol grubuna kıyasla anlamlı derecede artmıştı.
Sonuç: Yaşlı sıçanlar ve kontrol grubu arasında hipokampüs ve korteksteki genişlemiş kan damarları açısından anlamlı bir fark bulunmadı. Çalışmamızda yaşlı sıçanların hipokampüs ve korteks dokularında DAT, D1 ve D2 ekspresyonlarının artması dopaminin önemini vurgulayabilir. Verilerimiz yaşa bağlı motor ve bilişsel işlevlerdeki bozulmaların anlaşılmasında dopaminerjik yolaklara katkı sağlayabilir.

Keywords

Yaşlanan Beyin , D1 , D2 , Dopamin Taşıyıcısı , İmmünohistokimya

Investigation of the Effects of Monosodium Glutamate on Cortex and Hippocampus in Normal Aging Rats

Abstract

Objective: This study aims to investigate the expressions of the dopamine transporter (DAT), dopamine receptor 1 (D1), and dopamine receptor 2 (D2) in the cortex and hippocampus tissues of monosodium glutamate (MSG)-administered aged rats.
Method: Neuronal degeneration and dilated blood vessels in the hippocampus and cortex of the experimental groups’ brain tissues were evaluated by histopathological analysis. Immunoreactivity of DAT, D1, and D2 was determined by immunohistochemical analysis.
Results: Neuronal degeneration in the cortex was significantly higher in aged rats than in the control group. DAT, D1, and D2 reactivities in the hippocampus and cortex of aged rats were significantly increased compared to those in the control group.
Conclusion: No significant difference was found between the aged rats and the control group in terms of dilated blood vessels in the hippocampus and cortex. The increased DAT, D1, and D2 expressions in the hippocampus and cortex tissues of aged rats in our study may highlight the importance of dopamine. Our data may contribute to understanding age-related impairments in motor and cognitive functions through dopaminergic pathways.

Keywords

Aging Brain , D1 , D2 , Dopamine Transporter , Immunohistochemistry

Ethical Statement

The present study was reviewed and approved by the institutional ethics committee of the Hatay Mustafa Kemal University Animal Experiments Local Ethics Committee in March 2022 (IRB Approval Number: 143582).

Supporting Institution

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Thanks

The authors are grateful to all participants for their valuable contributions to this study.

References

• 1. Kroemer, G., Maier, A.B., Cuervo, A.M., Gladyshev, V.N., Ferrucci, L., Gorbunova, V., et al. (2025). From geroscience to precision geromedicine: Understanding and managing aging. Cell, 188(8), P2043-2062. Doi: 10.1016/j.cell.2025.03.011
• 2. Dorszewska, J. (2013). Cell biology of normal brain aging: Synaptic plasticity-cell death. Aging Clinical and Experimental Research, 25(1), 25–34. Doi: 10.1007/s40520-013-0004-2
• 3. Park, D. C., Reuter-Lorenz, P. (2009). The adaptive brain: Aging and neurocognitive scaffolding. Annual Review of Psychology, 60, 173–196. Doi: 10.1146/annurev.psych.59.103006.093656
• 4. Harada, C. N., Natelson Love, M. C., & Triebel, K. L. (2013). Normal cognitive aging. Clinics in Geriatric Medicine, 29(4), 737–752. Doi: 10.1016/j.cger.2013.07.002
• 5. Cadet, J. L., Jayanthi, S., T. McCoy, M., Beauvais, G., Sheng Cai, N. (2010). Dopamine D1 receptors, regulation of gene expression in the brain, and neurodegeneration. CNS Neurol Disord Drug Targets, 9(5), 526–538. Doi: 10.2174/187152710793361496
• 6. Beaulieu, J. M., & Gainetdinov, R.R. (2011). The physiology, signaling, and pharmacology of dopamine receptors. Pharmacological Reviews, 63(1), 182–217. Doi: 10.1124/pr.110.002642
• 7. Mishra, A., Singh, S., & Shukla, S. (2018). Physiological and functional basis of dopamine receptors and their role in neurogenesis: possible ımplication for Parkinson’s disease. Journal of Experimental Neuroscience, 12, 1–8. Doi: 10.1177/1179069518779829
• 8. Murman, D. L. (2015). The ımpact of age on cognition. Seminars in Hearing, 36(3), 111–121. Doi: 10.1055/s-0035-1555115
• 9. 9. Cools, R., Froböse, M., Aarts, E., & Hofmans, L. (2019). Dopamine and the motivation of cognitive control. Handb Clin Neurol, 163, 123–143. Doi: 10.1016/B978-0-12-804281-6.00007-0
• 10. 10. Long, C., Masmanidis, S.C. (2025). The learning primacy hypothesis of dopamine: reconsidering dopamine’s dual functions. Frontiers in Cellular Neuroscience, 19 – 2025, 1-10. doi:10.3389/fncel.2025.1538500.
• 11. Taylor WD, Zald DH, Felger JC, Christman S, Claassen DO, Horga G, et al. (2022). Influences of dopaminergic system dysfunction on late- life depression. Vol. 27, Molecular Psychiatry, 27(1), 180–191. Doi: 10.1038/s41380-021-01265-0
• 12. Erixon-Lindroth, N., Farde, L., Wahlin, T. B. R., Sovago, J., Halldin, C., & Bäckman, L. (2005). The role of the striatal dopamine transporter in cognitive aging. Psychiatry Research, 138(1), 1–12. Doi: 10.1016/j.pscychresns.2004.09.005
• 13. Danbolt, N. C., Furness, D. N., & Zhou, Y. (2016). Neuronal vs glial glutamate uptake: Resolving the conundrum. Neurochemistry International, 98, 29–45. Doi: 10.1016/j.neuint.2016.05.009
• 14. Sedlak, T. W., Paul, B. D., Parker, G. M., Hester, L. D., Snowman, A. M., Taniguchi, Y., Sawa, A. (2019). The glutathione cycle shapes synaptic glutamate activity. Proceedings of the National Academy of Sciences of the United States of America, 116(7), 2701–2706. Doi: 10.1073/pnas.1817885116
• 15. Zanfirescu, A., Ungurianu, A., Tsatsakis, A. M., Nițulescu, G. M., Kouretas, D., Veskoukis, A., et al. (2019). A review of the alleged health hazards of monosodium glutamate. Comprehensive Reviews in Food Science and Food Safety, 18(4), 1111–1134. Doi: 10.1111/1541-4337.12448
• 16. Geha, R. S., Beiser, A., Ren, C., Patterson, R., Greenberger, P. A., Grammer, L. C., et al. (2000). Glutamate safety in the food supply review of alleged reaction to monosodium glutamate and outcome of a multicenter double-blind placebo-controlled study. J. Nutr, 130, 1058– 1062.Doi: 10.1093/jn/130.4.1058S
• 17. Beas-Zárate, C., Morales-Villagran, A., Ortuño, S. D., & Feria-Velasco, A. (1995). Enhancement in dopamine uptake and release induced by monosodium l-glutamate from caudate nucleus under in vitro conditions. Comp Biochem Physiol A Physiol, 110(2), 151–157. Doi: 10.1016/0300-9629(94)00141-F
• 18. Tunca, Ü., Yalçın, A., Saygın, M., & Ellidağ, H. Y. (2019). Deneysel Egzersiz Uygulamasının Yaşlılık Sürecinde Etkileri. Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 6(4), 271–276. Doi: 10.34087/cbusbed.616028
• 19. Baytar, G., Kutlu, T., & Ogut, S. (2024). Investigation of potential protective effects of Betanin on experimental Monosodium Glutamate– induced toxicity in elderly rats. Revista Cientifica de La Facultad de Veterinaria, 34, 1–7. Doi: 10.52973/RCFCV-E34347
• 20. Strech, D., & Dirnagl, U. (2019). 3Rs missing: Animal research without scientific value is unethical. BMJ Open Science, 3(1). Doi: 10.1136/bmjos- 2018-000048
• 21. Depciuch, J., Jakubczyk, P., Paja, W., Sarzyński, J., Pancerz, K., Açıkel Elmas, M., et al. (2022). Apocynin reduces cytotoxic effects of monosodium glutamate in the brain: A spectroscopic, oxidative load, and machine learning study. Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 279, 121495. Doi: 10.1016/j.saa.2022.121495
• 22. Arslan, D., Ekinci, A., Arici, A., Bozdemir, E., Akil, E., & Ozdemir, H. H. (2017). Effects of Ecballium elaterium on brain in a rat model of sepsis- associated encephalopathy. Libyan Journal of Medicine, 12(1), 1369834. Doi:10.1080/19932820.2017.1369834
• 23. Okan, A., Doğanyiğit, Z., Eroğlu, E., Akyüz, E., & Demir, N. (2021). Immunoreactive definition of TNF- α, HIF-1 α, Kir6.2, Kir3.1 and M2 muscarinic receptor for cardiac and pancreatic tissues in a mouse model for type 1 diabetes. Life Sciences, 284, 119886. Doi: 10.1016/j.lfs.2021.119886
• 24. Okan, A., Demir, N., & Sozen, B. (2021). Unfolded protein response triggers differential apoptotic mechanisms in ovaries and early embryos exposed to maternal type 1 diabetes. Scientific Reports, 11(1), 1–13. Doi: 10.1038/s41598-021-92093-3
• 25. Wallace, D. R., & Dawson, R. (1990). Effect of age and monosodium- L-glutamate (MSG) treatment on neurotransmitter content in brain regions from male fischer-344 rats. Neurochemical Research, 15(9), 889–898. Doi: 10.1007/BF00965908
• 26. López-Pérez, S. J., Vergara, P., Ventura-Valenzuela, J. P., Ureña- Guerrero, M. E., Segovia, J., & Beas-Zárate, C. (2005). Modification of dopaminergic markers expression in the striatum by neonatal exposure to glutamate during development. International Journal of Developmental Neuroscience, 23(4), 335–342. Doi: 10.1016/j.ijdevneu.2004.12.010
• 27. Meister, B., Ceccatelli, S., Hökfelt, T., Andén, N. E., Andén, M., & Theodorsson, E. (1989). Neurotransmitters, neuropeptides and binding sites in the rat mediobasal hypothalamus: effects of monosodium glutamate (MSG) lesions. Experimental Brain Research, 76(2), 343–368. Doi: 10.1007/BF00247894
• 28. Arı, M., Erdogan, M. A., Erbaş, O. (2025). Investigation of the protective effects of dichloroacetic acid in a rat model of diabetic neuropathy. BMC Pharmacology & Toxicology, 26(1), 1-10. Doi:10.1186/s40360-025-00849-8
• 29. Cruz-Muros, I., Afonso-Oramas, D., Abreu, P., Pérez-Delgado, M. M., Rodríguez, M., & González-Hernández, T. (2009). Aging effects on the dopamine transporter expression and compensatory mechanisms. Neurobiology of Aging, 30(6), 973–986. Doi: 10.1016/j.neurobiolaging.2007.09.009
• 30. Salvatore, M. F., Apparsundaram, S., & Gerhardt, G. A. (2003). Decreased plasma membrane expression of striatal dopamine transporter in aging. Neurobiology of Aging, 24(8), 1147–1154. Doi: 10.1016/S0197-4580(03)00129-5
• 31. Li, H., Hirano, S., Furukawa, S., Nakano, Y., Kojima, K., Ishikawa, A., et al. (2020). The relationship between the striatal dopaminergic neuronal and cognitive function with aging. Frontiers in Aging Neuroscience, 12, 1–10. Doi: 10.3389/fnagi.2020.00041
• 32. Troiano, A. R., Schulzer, M., De La Fuente-Fernandez, R., Mak, E., Mckenzie, J., Sossi, V., et al. (2010). Dopamine transporter PET in normal aging: Dopamine transporter decline and its possible role in preservation of motor function. Synapse, 64(2), 146–151. Doi: 10.1002/syn.20708
• 33. Lubec, J., Kalaba, P., Hussein, A. M., Feyissa, D. D., Kotob, M. H., Mahmmoud, R. R., et al. (2021). Reinstatement of synaptic plasticity in the aging brain through specific dopamine transporter inhibition. Molecular Psychiatry, 26(12), 7076-7090. Doi: 10.1038/s41380-021-01214-x
• 34. Turner, M. P., Fischer, H., Sivakolundu, D. K., Hubbard, N. A., Zhao, Y., Rypma, B., et al. (2020). Age-differential relationships among dopamine D1 binding potential, fusiform BOLD signal, and face- recognition performance. NeuroImage, 206, 116232. Doi: 10.1016/j.neuroimage.2019.116232
• 35. Rieckmann, A., Karlsson, S., Karlsson, P., Brehmer, Y., Fischer, H., Farde, L., et al. (2011). Dopamine D1 receptor associations within and between dopaminergic pathways in younger and elderly adults: Links to cognitive performance. Cerebral Cortex, 21(9), 2023–2032. Doi: 10.1093/cercor/bhq266
• 36. MacDonald, S. W. S., Karlsson, S., Rieckmann, A., Nyberg, L., & Bäckman, L. (2012). Aging-related increases in behavioral variability: Relations to losses of dopamine D 1 receptors. Journal of Neuroscience, 32(24), 8186–8191. Doi: 10.1523/JNEUROSCI.5474-11.2012
• 37. Keeler, B. E., Lallemand, P., Patel, M. M., de Castro Brás, L. E., & Clemens, S. (2016). Opposing aging-related shift of excitatory dopamine D1 and inhibitory D3 receptor protein expression in striatum and spinal cord. Journal of Neurophysiology, 115(1), 363–369. Doi: 10.1152/jn.00390.2015
• 38. Sakata, M., Farooqui, S. M., & Prasad, C. (1992). Post-transcriptional regulation of loss of rat striatal D2 dopamine receptor during aging. Brain Research, 575(2), 309–314. Doi:10.1016/0006-8993(92)90095-Q
• 39. Saroja, S. R., Kim, E. J., Shanmugasundaram, B., Höger, H., & Lubec, G. (2014). Hippocampal monoamine receptor complex levels linked to spatial memory decline in the aging C57BL/6J. Behavioural Brain Research, 264, 1–8. Doi: 10.1016/j.bbr.2014.01.042
• 40. Li, S. C., Papenberg, G., Nagel, I. E., Preuschhof, C., Schröder, J., Nietfeld, W., et al. (2013). Aging magnifies the effects of dopamine transporter and D2 receptor genes on backward serial memory. Neurobiology of Aging, 34(1), 358.e1-358.e10. Doi: 10.1016/j.neurobiolaging.2012.08.001