Expression of GABAAα1, GABAB1, and mGluR2 receptors in the lateral geniculate body of male neonates born to diabetic rats

Document Type : Original Article

Authors

1 Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Nervous System Stem Cell Research Center, Semnan University of Medical Sciences, Semnan, Iran;Department of Anatomical Sciences, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

3 Regenerative Medicine, Organ Procurement and transplantation Multidisciplinary Center, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

4 Medical Genetic Research Center (MGRC), School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Diabetes during gestation is one of the most common pregnancy complications and has adverse effects on offspring, including a negative impact on the offspring’s central nervous system (CNS). Diabetes is a metabolic disease associated with visual impairment. Due to the importance of the lateral geniculate body (LGB) in the visual pathway, the present study examined the effect of maternal diabetes on the expression of gamma-aminobutyric acid (GABAAα1 and GABAB1) and metabotropic Glutamate (mGlu2) receptors in the LGB of male neonates of diabetic rats.
Materials and Methods: Diabetes was induced in female adult rats by a single intraperitoneal dose of streptozotocin (STZ) 65 (mg/kg). In the Insulin-treated diabetic rats, diabetes was controlled by subcutaneous NPH-insulin injection daily. After mating and delivery, male offspring were killed by carbon dioxide gas inhalation at P0, P7, and P14 (postnatal days 0, 7, and 14). The expression of GABAAα1, GABAB1, and mGluR2 in the LGB of male neonates was determined using the immunohistochemistry (IHC) method.
Results: The expression of GABAAα1 and GABAB1 was significantly reduced, whereas the expression of mGluR2 was markedly increased in the diabetic group compared with the control and insulin-treated groups at P0, P7, and P14.
Conclusion: The results of the present study showed that induction of diabetes altered the expression of GABAAα1, GABAB1, and mGluR2 in the LGB of male neonates born to diabetic rats at P0, P7, and P14. Moreover, insulin treatment could reverse these effects of diabetes.

Keywords

Main Subjects


1. Lotfi N, Hami J, Hosseini M, Haghir D, Haghir H. Diabetes during pregnancy enhanced neuronal death in the hippocampus of rat offspring. Int J Dev Neurosci 2016;51:28-35.
2. Ma WX, Tang J, Lei ZW, Li CY, Zhao LQ, Lin C, et al. Potential biochemical mechanisms of brain injury in diabetes mellitus. Aging Dis 2020;11:978-987.
3. Fleming MD, Benca RM, Behan M. Retinal projections to the subcortical visual system in congenic albino and pigmented rats. Neuroscience 2006;143:895-904.
4. LeVere T. The primary visual system of the rat: A primer of its anatomy. Physiologic Psychol 1978;6:142-169.
5. Jonak K, Krukow P, Jonak KE, Radzikowska E, Baj J, Niedziałek A, et al. Decreased volume of lateral and medial geniculate nuclei in patients with LHON disease-7 tesla MRI study. J Clin Med 2020;9:2914-2927.
6. Kvale I, Fosse V, Fonnum F. Development of neurotransmitter parameters in lateral geniculate body, superior colliculus and visual cortex of the albino rat. Dev Brain Res 1983;7:137-145.
7. d’Almeida OC, Violante IR, Quendera B, Moreno C, Gomes L, Castelo-Branco M. The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes. PloS One 2020;15:e0240907-240923.
8. Chebib M, Johnston GA. The ‘ABC’ of GABA receptors: A brief review. Clin Exp Pharmacol Physiol 1999;26:937-940.
9. Terunuma M. Diversity of structure and function of GABAB receptors: A complexity of GABAB-mediated signaling. Proc Jpn Acad Ser B Phys Biol Sci 2018;94:390-411.
10. Binns K, Salt T. Different roles for GABAA and GABAB receptors in visual processing in the rat superior colliculus. J  Physiol 1997;504:629-639.
11. Nutt D. GABA A receptors: Subtypes, regional distribution, and function. J Clin Sleep Med 2006;2:S7-S11.
12. Papasergi-Scott MM, Robertson MJ, Seven AB, Panova O, Mathiesen JM, Skiniotis G. Structures of metabotropic GABA B receptor. Nature 2020;584:310-314.
13. Antony S, Peeyush Kumar T, Kuruvilla KP, George N, Paulose C. Decreased GABA receptor binding in the cerebral cortex of insulin induced hypoglycemic and streptozotocin induced diabetic rats. Neurochem Res 2010;35:1516-1521.
14. Russell JW, Anjaneyulu M, Berent-Spillson A. Metabotropic glutamate receptors (mGluRs) and diabetic neuropathy. Curr Drug Targets 2008;9:85-93.
15. Kim J-H, Marton J, Ametamey SM, Cumming P. A review of molecular imaging of glutamate receptors. Molecules 2020;25:4749-4790.
16. Mazzitelli M, Palazzo E, Maione S, Neugebauer V. Group II metabotropic glutamate receptors: Role in pain mechanisms and pain modulation. Front Mol Neurosci 2018;11:383-393.
17. Govindaiah G, Venkitaramani DV, Chaki S, Cox CL. Spatially distinct actions of metabotropic glutamate receptor activation in dorsal lateral geniculate nucleus. J Neurophysiol 2012;107:1157-1163.
18. Liu Z, Han Y, Zhao H, Luo W, Jia L, Wang Y. Glu-mGluR2/3-ERK signaling regulates apoptosis of hippocampal neurons in diabetic-depression model rats. Evid Based Complement Alternat Med 2019;2019:3710363-3710371.
19. Chen H, Wang M, Xia L, Dong J, Xu G, Wang Z, et al. New evidence of central nervous system damage in diabetes mellitus: Impairment of fine visual discrimination. Diabetes 2022;71:1772-1784.
20. Lau JC, Kroes RA, Moskal JR, Linsenmeier RA. Diabetes changes expression of genes related to glutamate neurotransmission and transport in the Long-Evans rat retina. Mol Vis 2013;19:1538-1553.
21. Furman BL. Streptozotocin‐induced diabetic models in mice and rats. Curr Protoc Pharmacol 2021;1:e78-78.
22. Rezazadeh H, Sharifi MR, Sharifi M, Soltani N. Gamma-aminobutyric acid attenuates insulin resistance in type 2 diabetic patients and reduces the risk of insulin resistance in their offspring. Biomed Pharmacother 2021;138:111440-111452.
23. Abbasi F, Baradaran R, Khoshdel-Sarkarizi H, Kargozar S, Hami J, Mohammadipour A, et al. Distribution pattern of nicotinic acetylcholine receptors in developing cerebellum of rat neonates born of diabetic mothers. J Chem Neuroanat 2020;108:101819.
24. Haghir H, Rezaee AAR, Sankian M, Kheradmand H, Hami J. The effects of induced type-I diabetes on developmental regulation of insulin & insulin like growth factor-1 (IGF-1) receptors in the cerebellum of rat neonates. Metab Brain Dis 2013;28:397-410.
25. Ye Z, Yu X, Houston CM, Aboukhalil Z, Franks NP, Wisden W, et al. Fast and slow inhibition in the visual thalamus is influenced by allocating GABAa receptors with different γ subunits. Front Cell Neurosci 2017;11:95-104.
26. Vahidinia Z, Alipour N, Atlasi MA, Naderian H, Beyer C, Azami Tameh A. Gonadal steroids block the calpain-1-dependent intrinsic pathway of apoptosis in an experimental rat stroke model. Neurol Res 2017;39:54-64.
27. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates 2005; San Diego. Academic Press.
28. Ramachandra R, Subramanian T. Atlas of the neonatal rat brain: CRC press; 2016.
29. Carpi-Santos R, Maggesissi R, von Seehausen M, Calaza K. Retinal exposure to high glucose condition modifies the GABAergic system: Regulation by nitric oxide. Exp Eye Res 2017;162:116-125.
30. Santiago AR, Gaspar JM, Baptista FI, Cristóvão AJ, Santos PF, Kamphuis W, et al. Diabetes changes the levels of ionotropic glutamate receptors in the rat retina. Mol Vis 2009;15:1620-1630.
31. Honda M, Inoue M, Okada Y, Yamamoto M. Alteration of the GABAergic neuronal system of the retina and superior colliculus in streptozotocin-induced diabetic rat. Kobe J Med Sci 1998;44:1-8.
32. Govindaiah G, Cox CL. Metabotropic glutamate receptors differentially regulate GABAergic inhibition in thalamus. J Neurosci 2006;26:13443-13453.
33. Perreault MC, Qin Y, Heggelund P, Zhu JJ. Postnatal development of GABAergic signalling in the rat lateral geniculate nucleus: presynaptic dendritic mechanisms. J Physiol 2003;546:137-148.
34. Yoon JH, Maddock RJ, Rokem A, Silver MA, Minzenberg MJ, Ragland JD, et al. GABA concentration is reduced in visual cortex in schizophrenia and correlates with orientation-specific surround suppression. J Neurosci 2010;30:3777-3781.
35. Tu LL, Sun Q, Wei LL, Shi J, Li JP. Upregulation of GABA receptor promotes long‑term potentiation and depotentiation in the hippocampal CA1 region of mice with type 2 diabetes mellitus. Exp Ther Med 2019;18:2429-2436.
36. Biju M, Paulose C. Brain glutamate dehydrogenase changes in streptozotocin diabetic rats as a function of age. Biochem Mol Biol Int 1998;44:1-7.
37. Sadeghi A, Esfandiary E, Hami J, Khanahmad H, Hejazi Z, Razavi S. Effect of maternal diabetes on gliogensis in neonatal rat hippocampus. Adv Biomed Res 2016;5:142-148.
38. Sah R, Galeffi F, Ahrens R, Jordan G, Schwartz‐Bloom RD. Modulation of the GABAA‐gated chloride channel by reactive oxygen species. J neurochem 2002;80:383-391.
39. Muriach M, Flores-Bellver M, Romero FJ, Barcia JM. Diabetes and the brain: Oxidative stress, inflammation, and autophagy. Oxid Med Cell Longev 2014;2014:102158-102166.
40. Van der Vliet A, Bast A. Effect of oxidative stress on receptors and signal transmission. Chem Biol Interact 1992;85:95-116.
41. Ikonomovic S, Kharlamov E, Manev H, Ikonomovic MD, Grayson DR. GABA and NMDA in the prevention of apoptotic-like cell death in vitro. Neurochem Int 1997;31:283-290.
42. Chen CY, Ling Eh, Horowitz JM, Bonham AC. Synaptic transmission in nucleus tractus solitarius is depressed by Group II and III but not Group I presynaptic metabotropic glutamate receptors in rats. J Physiol 2002;538:773-786.
43. Caruso C, Bottino M, Pampillo M, Pisera D, Jaita G, Duvilanski B, et al. Glutamate induces apoptosis in anterior pituitary cells through group II metabotropic glutamate receptor activation. Endocrinology 2004;145:4677-4684.
44. Godwin DW, Vaughan JW, Sherman SM. Metabotropic glutamate receptors switch visual response mode of lateral geniculate nucleus cells from burst to tonic. J Neurophysiol 1996;76:1800-1816.
45. Vuong B, Odero G, Rozbacher S, Stevenson M, Kereliuk SM, Pereira TJ, et al. Exposure to gestational diabetes mellitus induces neuroinflammation, derangement of hippocampal neurons, and cognitive changes in rat offspring. J Neuroinflam 2017;14:1-13.
46. Taylor DL, Jones F, Kubota ESCS, Pocock JM. Stimulation of microglial metabotropic glutamate receptor mGlu2 triggers tumor necrosis factor α-induced neurotoxicity in concert with microglial-derived Fas ligand. J Neurosci 2005;25:2952-2964.
47. Balakrishnan S, Kumar P, Paulose C. Glutamate (mGluR-5) gene expression in brain regions of streptozotocin induced diabetic rats as a function of age: role in regulation of calcium release from the pancreatic islets in vitro. J Biomed Sci 2009;16:1-11.
48. Fagni L, Chavis P, Ango F, Bockaert J. Complex interactions between mGluRs, intracellular Ca2+ stores and ion channels in neurons. Trends Neurosci 2000;23:80-88.
49. Gleichmann M, Mattson MP. Neuronal calcium homeostasis and dysregulation. Antioxid Redox Signal 2011;14:1261-1273.
50. Johnson ME, Gores GJ, Uhl CB, Sill JC. Cytosolic free calcium and cell death during metabolic inhibition in a neuronal cell line. J Neurosci 1994;14:4040-4049.