Effects of Elevated D-Glucose Concentrations on AMPA and NMDA Re ceptor Activity in Modeled Hyperglycemia in Brain Slices
https://doi.org/10.33647/2074-5982-21-1-34-45
Abstract
The effects of various D-glucose concentrations (0.5; 1; 3; 5; 7; 10; 12; 14; 17; 20; 22; and 25 mM) were studied using brain slices of the rat olfactory cortex to determine changes in the activities of AMPA and NMDA ionotropic glutamatergic mechanisms. The dependence of the amplitudes of the AMPA and NMDA potentials on D-glucose concentrations was dome-shaped. Lower concentrations (0.5; 1; 3; 5 mM) caused a progressive increase in the amplitudes of AMPA and NMDA potentials. Under D-glucose concentra tions in the extracellular medium of 7 and 10 mM, the amplitudes of AMPA and NMDA potentials were maximal and stable. Under a D-glucose concentration of 14 mM, the activities of AMPA and NMDA mechanisms decreased and, following a further increase in carbon, were irreversibly blocked. Long-term post-tetanic potentiation (model of non-associative learning) developed only at a D-glucose concentration of 10 mM. Heat shock protein (Mw70 kDa) protected the activities of AMPA and NMDA mechanisms from the negative effects of high hyperglycemic D-glucose concentration of 14 mM. The data obtained indicate the response of AMPA and NMDA mechanisms during the development of hyperglycemia. This model can be used to search for substances to protect neuronal mechanisms in the nervous tissue during the develop ment of hyperglycemic diabetes mellitus.
Supporting agencies: the study was supported by state funding allocated to the Pavlov Institute of Physiology Russian Academy of Sciences (No. 1023032400236-8-3.1.4).
About the Author
A. A. Mokrushin
I.P. Pavlov Institute of Physiology of the Russian Academy of Sciences
Russian Federation
Russian Federation
Anatoliy A. Mokrushin, Dr. Sci. (Biol.)
19903, St. Petersburg, Makarova Emb., 6
References
1. Mityushov M.I., Emelianov N.A., Mokrushin A.A., Voyner I.A., Bagaeva T.R. Perezhivayushchij srez moz ga kak ob"ekt nejrofiziologicheskogo i nejrohimichesko go issledovaniya [The surviving brain slice as an object of neurophysiological and neurochemical research]. Leningrad: Nauka Publ., 1986:127. (In Russian).
2. Mokrushin A.A. Peptid-zavisimye mekhanizmy nejronal'noj plastichnosti v obonyatel'noj kore [Peptide-dependent mechanisms of neuronal plasticity in the olfactory cortex]: diss. … Dr. of Biol. Sci. St. Petersburg: I.P. Pavlov Institute of Physiology of the Russian Academy of Sciences, 1997:397. (In Russian).
3. Mokrushin A.A., Pavlinova L.I., Guzhova I.V., Margu lis B.A. Effekty ekzogennogo belka teplovogo shoka (HSP70) na glutamatergicheskuyu sinapticheskuyu pere dachu v obonyatel'noj kore mozga krys in vitro [Effects of Exogenous heat shock protein (Hsp70) on glutamater gic synaptic transmission in rat olfactory cortex in vitro]. Dokl. Acad. of Sci. 2004;395(4):551–553. (In Russian).
4. Mokrushin A.A., Borovikov S.E. Ustanovka dlya izucheniya gipo termicheskin effektov na perezhivayushchih srezah mozga teplokrovnyh [Installation for the study of hypothermic effects on the brain surviving slices of warm-blooded]. Mezhdunarodnyj zhurnal prikladnyh fundamental`nynh issledovanij [International Journal of Applied Fundamental Research]. 2017;2(2):214–217. (In Russian).
5. Biessels G.J., Kamal A., Ramakers G.M. Place learn ing and hippocampal synaptic plasticity in streptozoto cin-induced diabetes rats. Diabetes. 1996;45:1259–1267.
6. Brossaud J., Bosch-Bouju C., Marissal-Arvy N., Campas Lebecque M.-N., Webster S.P., Walker B.R., Moisan W.-P. Memory deficits in a juvenile rat model of type 1 di abetes are due to excess 11β-HSD1 activity, which is upregulated by high glucose concentrations rather than insulin deficiency. Diabetologia. 2023;66(9):1735–1747. DOI: 10.1007/s00125-023-05942-3.
7. Cukierman T., Gerstein H.C., Williamson J.D. Cognitive decline and dementia in diabetes–systematic overview of prospective observational studies. Diabetologia. 2005;48:2460–2469. DOI: 10.1007/s00125-005-0023-4.
8. Di Mario U., Morrano S., Valle E. Electrophysiological alteration of the central nervous system in diabetes mel litus. Diabetes Metab. Rev. 1995;11:259–277.
9. Fang F., Xu L., Zhang R., Liu L., Tang M. Neuronal Hyperactivity in the Hippocampus during the Early Stage of Streptozotocin-Induced Type 1 Diabetes in Mice. Neuroendocrinology. 2024;114(4):356–364.
10. Garcia-Magro N., Mesa-Lombardo A., Barros-Zulaica N., Nuñer Á., Artola A., Kamal A., Gispen W.H. Diabetes mellitus concomitantly facilitates the induction of long term depression and inhibits that of long-term potentia tion in hippocampus. Eur. J. Neurosci. 2005;22:169–178. DOI: 10.1111/j.1460-9568.2005.04205.x.
11. Garcia-Magro N., Mesa-Lombardo A., Barros Zulaica N. Impairment of synaptic plasticity in the pri mary somatosensory cortex in a model of diabetic mice. Front Cell Neurosci. 2024;30:18–25. DOI: 10.3389/fncel.2024.1444395.
12. Gispen W.H., Biessels G.J. Cognition and synap tic plasticity in diabetes mellitus. Trends Neurosci. 2000;23:542–549.
13. Gruettert R., Novothy E.J., Boulware S.D., Rothman D.L. Direct measurement of brain glucose concentrations in humans by 13 C NMR spectroscopy. Proc. Natl. Acad. Sci. USA. 1992;89:1109–1112.
14. Hristov M., Nankova A., Andreeva-Gateva P. Alterations of the glutamatergic system in diabetes mellitus. Metab. Brain Dis. 2023;39(2):321–333. DOI: 10.1007/s11011023-01299-z.
15. Liu D., Zhang H., Gu W., Zhang M. Effects of exposure to high glucose on primary Cultured hippocampal neu rons: involvement of intracellular ROS accumulation. Neurological Science. 2014;35(6):831–837.
16. Mokrushin A.A. Mystixin-7 mini-peptide protects iono tropic glutamatergic mechanisms against oxygen-glucose deprivation in vitro. Neuropeptides. 2015;54:163–168.
17. Rodriguez-Perez M.D., Perez de Algaba I., Martin Aurioles E. Dihydroxyphenylglycol In Type-1-like Diabetic Rats-Influence of the Hydroxytyrosol/3',4 dihydroxyphenylglycol Ratio. Nutrients. 2022;14(6): 1146. DOI: 10.3390/nu14061146.
18. Sasaki-Hamada S., Sacai H., Oka J.-I. Diabetes onset influences hippocampal synaptic plasticity in strepto zotocin-treated rats. Neuroscience. 2012;227:293–304. DOI: 10.1016/j.neuroscience.2012.09.081.
19. Silver I.A., Ereciаska M. Extracellular Glucose Concentration in Mammalian Brain: Continuous Monitoring of Changes during Increased Neuronal Activity and upon Limitation in Oxygen Supply in Normo-, Hypo-, and Hyperglycemic Animals. The Journal of Neuroscience. 1994;14(8):5068–5076.
20. Trudeau F., Sylvain G., Guy M. Hippocampal synaptic plasticity and glutamate receptor regulation: influences of diabetes mellitus. Eur. J. Pharmacol. 2004;490(1 3):177–186. DOI: 10.1016/j.ejphar.2004.02.055.
21. Valastro B., Cossette J., Lavoie N., Gagnon S., Trudeau F. Up-regulation of glutamate receptors is associated with LTP defects in the early stages of diabetes mellitus. Dibetologia. 2002;45:642–650. DOI: 10.1007/s00125-002-0818-5.
22. Volianskis A., France G., Jensen M.S., Bortolotto Z.A., Jane D.E., Collingridge G.L. Long-term potentiation and the role of N-methyl-d-aspartate receptors. Brain Research. 2015;1621:5-16. DOI: 10.1016/J.Brainres. 2015.01.016.
23. Yin H., Wang W., Yu W., Li J. Changes in Synaptic Plasticity and Glutamate Receptors in Type 2 Diabetic KK-Ay Mice. Journal of Alzheimer's disease. 2017;57(4):1207–1220. DOI: 10.3233/JAD-160858.
24. Zanotto C., Hansen F., Galland F., Batassini C. Glutama-tergic Alterations in STZ-Induced Diabetic Rats Are Reversed by Exendin-4. Molecular Neurobiol. 2019;56(5):3538–3551. DOI: 10.1007/s12035-018-1320-5.
Review
For citations:
Mokrushin A.A. Effects of Elevated D-Glucose Concentrations on AMPA and NMDA Re ceptor Activity in Modeled Hyperglycemia in Brain Slices. Journal Biomed. 2025;21(1):34-45. (In Russ.) https://doi.org/10.33647/2074-5982-21-1-34-45
Views:
131
Email this article 
