Volume 28, Issue 4 (December 2024)                   Physiol Pharmacol 2024, 28(4): 419-429 | Back to browse issues page


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Beheshti S, Kooravand N. Differential changes in the quantity of the hippocampal glial connexins mRNAs during memory consolidation. Physiol Pharmacol 2024; 28 (4) : 5
URL: http://ppj.phypha.ir/article-1-2167-en.html
Abstract:   (634 Views)

Introduction: It is known that glial cells are crucial for memory formation. Glial cells and neurons interconnect via gap junction channels made of connexin (Cx) proteins. Glial connexins were shown to be involved in memory formation. However, the expression profile of different glial connexins was not measured during memory consolidation. Cx43 and Cx30 are expressed in astrocytes, whereas Cx32 is expressed in oligodendrocytes. We quantified the messenger RNA (mRNA) levels of the hippocampal Cx30, Cx32, and Cx43 throughout the consolidation stage of fear or spatial memory.
Methods: Male Wistar rats were distributed into eight groups of four each. To assess the spatial or fear memory consolidation, the Morris water maze and passive avoidance task were utilized. At different time intervals (one, three, and twenty-four hours) following the training sessions, rats were sacrificed and the hippocampi were isolated and frozen instantly in liquid nitrogen. A quantitative real-time polymerase chain reaction (PCR) was employed to measure mRNA levels of the target genes.
Results: The results revealed that Cx43 and Cx32 downregulated significantly, one or three hours after training in the inhibitory avoidance model. In the Morris water maze, Cx43 expression was upregulated three hours after training. The expression of Cx30 did not exhibit significant alterations in either of the experimental assays.
Conclusion: The results indicate the crucial, but differential role of the hippocampal Cx32 and Cx43 during fear or spatial memory consolidation. The exact outcomes of these potential changes need to be clarified.

Article number: 5
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References
1. Abel T, Lattal K M. Molecular mechanisms of memory acquisition, consolidation and retrieval. Current Opinion in Neurobiology 2001; 11: 180-187. [DOI:10.1016/S0959-4388(00)00194-X]
2. Beheshti S, Aslani N. Local injection of d-lys-3-GHRP-6 in the rat amygdala, dentate gyrus or ventral tegmental area impairs memory consolidation. Neuropeptides 2018; 67: 20-26. [DOI:10.1016/j.npep.2017.11.002]
3. Beheshti S, Dehestani H. Differential expression levels of the hippocampal ghrelin and its receptor mRNA during memory consolidation. Behav Brain Res 2021; 408: 113270. [DOI:10.1016/j.bbr.2021.113270]
4. Beheshti S, Ghorbanpour Skakakomi A, Ghaedi K, Dehestani H. Frankincense upregulates the hippocampal calcium/calmodulin kinase II-α during development of the rat brain and improves memory performance. Int J Dev Neurosci 2018; 69: 44-48. [DOI:10.1016/j.ijdevneu.2018.06.011]
5. Beheshti S, Zeinali R, Esmaeili A. Rapid upregulation of the hippocampal connexins 36 and 45 mRNA levels during memory consolidation. Behav Brain Res 2017; 320: 85-90. [DOI:10.1016/j.bbr.2016.11.048]
6. Chaaya N, Battle A R, Johnson L R. An update on contextual fear memory mechanisms: Transition between Amygdala and Hippocampus. Neurosci Biobehav Rev 2018; 92: 43-54. [DOI:10.1016/j.neubiorev.2018.05.013]
7. Chever O, Lee C-Y, Rouach N. Astroglial connexin43 hemichannels tune basal excitatory synaptic transmission. The Journal of Neuroscience 2014; 34: 11228-11232. [DOI:10.1523/JNEUROSCI.0015-14.2014]
8. Cotrina M L, Lin J H, Alves-Rodrigues A, Liu S, Li J, Azmi-Ghadimi H, et al. Connexins regulate calcium signaling by controlling ATP release. Proc Natl Acad Sci U S A 1998; 95: 15735-40. [DOI:10.1073/pnas.95.26.15735]
9. De Pina-Benabou M H, Srinivas M, Spray D C, Scemes E. Calmodulin kinase pathway mediates the K+-induced increase in Gap junctional communication between mouse spinal cord astrocytes. Journal of Neuroscience 2001; 21: 6635-6643. [DOI:10.1523/JNEUROSCI.21-17-06635.2001]
10. Dupret D, Revest J M, Koehl M, Ichas F, De Giorgi F, Costet P, et al. Spatial relational memory requires hippocampal adult neurogenesis. PLoS One 2008; 3: e1959. [DOI:10.1371/journal.pone.0001959]
11. Escartin C, Rouach N. Astroglial networking contributes to neurometabolic coupling. Frontiers in neuroenergetics 2013; 5: 4-4. [DOI:10.3389/fnene.2013.00004]
12. Frisch C, Theis M, De Souza Silva M A, Dere E, Söhl G, Teubner B, et al. Mice with astrocyte-directed inactivation of connexin43 exhibit increased exploratory behaviour, impaired motor capacities, and changes in brain acetylcholine levels. European Journal of Neuroscience 2003; 18: 2313-2318. [DOI:10.1046/j.1460-9568.2003.02971.x]
13. Giaume C. Astroglial wiring is adding complexity to neuroglial networking. Frontiers in neuroenergetics 2010; 2: 129. [DOI:10.3389/fnene.2010.00129]
14. Griemsmann S, Höft S P, Bedner P, Zhang J, von Staden E, Beinhauer A, et al. Characterization of panglial gap junction networks in the thalamus, neocortex, and hippocampus reveals a unique population of glial cells. Cereb Cortex 2015; 25: 3420-33. [DOI:10.1093/cercor/bhu157]
15. He J-T, Li X-Y, Yang L, Zhao X. Astroglial connexins and cognition: memory formation or deterioration? Bioscience reports 2020; 40: BSR20193510. [DOI:10.1042/BSR20193510]
16. Hertz L, Chen Y. Editorial: All 3 types of glial cells are important for memory formation. Frontiers in Integrative Neuroscience 2016; 10. [DOI:10.3389/fnint.2016.00031]
17. Jammal L, Whalley B, Barkai E. Learning-induced modulation of the effect of neuroglial transmission on synaptic plasticity. J Neurophysiol 2018; 119: 2373-2379. [DOI:10.1152/jn.00101.2018]
18. Jessberger S, Clark R E, Broadbent N J, Clemenson G D, Jr., Consiglio A, Lie D C, et al. Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats. Learn Mem 2009; 16: 147-54. [DOI:10.1101/lm.1172609]
19. Kandel E R. The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB. Molecular Brain 2012; 5: 14. [DOI:10.1186/1756-6606-5-14]
20. Koulakoff A, Ezan P, Giaume C. Neurons control the expression of connexin 30 and connexin 43 in mouse cortical astrocytes. Glia 2008; 56: 1299-311. [DOI:10.1002/glia.20698]
21. Kristian Enkvist M, McCarthy K D. Astroglial gap junction communication is increased by treatment with either glutamate or high K+ concentration. Journal of neurochemistry 1994; 62: 489-495. [DOI:10.1046/j.1471-4159.1994.62020489.x]
22. Lalo U, Rasooli-Nejad S, Pankratov Y. Exocytosis of gliotransmitters from cortical astrocytes: implications for synaptic plasticity and aging. Journal 2014. [DOI:10.1042/BST20140163]
23. Liebmann M, Stahr A, Guenther M, Witte O W, Frahm C. Astrocytic Cx43 and Cx30 differentially modulate adult neurogenesis in mice. Neurosci Lett 2013; 545: 40-5. [DOI:10.1016/j.neulet.2013.04.013]
24. Linsambarth S, Carvajal F J, Moraga-Amaro R, Mendez L, Tamburini G, Jimenez I, et al. Astroglial gliotransmitters released via Cx43 hemichannels regulate NMDAR-dependent transmission and short-term fear memory in the basolateral amygdala. Faseb j 2022; 36: e22134. [DOI:10.1096/fj.202100798RR]
25. Livak K J, Schmittgen T D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25: 402-8. [DOI:10.1006/meth.2001.1262]
26. Lorenzini C A, Baldi E, Bucherelli C, Sacchetti B, Tassoni G. Role of dorsal hippocampus in acquisition, consolidation and retrieval of rat’s passive avoidance response: a tetrodotoxin functional inactivation study. Brain Res 1996; 730: 32-9. [DOI:10.1016/0006-8993(96)00427-1]
27. Lutz S E, Zhao Y, Gulinello M, Lee S C, Raine C S, Brosnan C F. Deletion of astrocyte connexins 43 and 30 leads to a dysmyelinating phenotype and hippocampal CA1 vacuolation. Journal of Neuroscience 2009; 29: 7743-7752. [DOI:10.1523/JNEUROSCI.0341-09.2009]
28. McCracken C B, Roberts D C. A single evoked afterdischarge produces rapid time-dependent changes in connexin36 protein expression in adult rat dorsal hippocampus. Neuroscience letters 2006; 405: 84-88. [DOI:10.1016/j.neulet.2006.06.025]
29. Meunier C, Wang N, Yi C, Dallerac G, Ezan P, Koulakoff A, et al. Contribution of astroglial Cx43 hemichannels to the modulation of glutamatergic currents by d-serine in the mouse prefrontal cortex. J Neurosci 2017; 37: 9064-9075. [DOI:10.1523/JNEUROSCI.2204-16.2017]
30. Nagy J I, Rash J E. Connexins and gap junctions of astrocytes and oligodendrocytes in the CNS. Brain Research Reviews 2000; 32: 29-44. [DOI:10.1016/S0165-0173(99)00066-1]
31. Naus C C, Bechberger J F, Zhang Y, Venance L, Yamasaki H, Juneja S C, et al. Altered gap junctional communication, intercellular signaling, and growth in cultured astrocytes deficient in connexin43. Journal of neuroscience research 1997; 49: 528-540. h [DOI:10.1002/(SICI)1097-4547(19970901)49:53.0.CO;2-D]
32. Navarrete M, Perea G, de Sevilla D F, Gómez-Gonzalo M, Núñez A, Martín E D, et al. Astrocytes mediate in vivo cholinergic-induced synaptic plasticity. PLoS biology 2012; 10: e1001259. [DOI:10.1371/journal.pbio.1001259]
33. Niu J, Li T, Yi C, Huang N, Koulakoff A, Weng C, et al. Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage. J Cell Sci 2016; 129: 1902-14. [DOI:10.1242/jcs.178731]
34. Opitz B. Memory function and the hippocampus. Front Neurol Neurosci 2014; 34: 51-9. [DOI:10.1159/000356422]
35. Oyamada M, Oyamada Y, Takamatsu T. Regulation of connexin expression. Biochim Biophys Acta 2005; 1719: 6-23. [DOI:10.1016/j.bbamem.2005.11.002]
36. Panchin Y V. Evolution of gap junction proteins - the pannexin alternative. Journal of Experimental Biology 2005; 208: 1415-1419. [DOI:10.1242/jeb.01547]
37. Pannasch U, Vargová L, Reingruber J, Ezan P, Holcman D, Giaume C, et al. Astroglial networks scale synaptic activity and plasticity. Proceedings of the national academy of sciences 2011; 108: 8467-8472. [DOI:10.1073/pnas.1016650108]
38. Pasti L, Volterra A, Pozzan T, Carmignoto G. Intracellular calcium oscillations in astrocytes: a highly plastic, bidirectional form of communication between neurons and astrocytes in situ. J Neurosci 1997; 17: 7817-30. [DOI:10.1523/JNEUROSCI.17-20-07817.1997]
39. Rash J E, Yasumura T, Dudek F E, Nagy J I. Cell-specific expression of connexins and evidence of restricted gap junctional coupling between glial cells and between neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 2001; 21: 1983-2000. [DOI:10.1523/JNEUROSCI.21-06-01983.2001]
40. Redish A D, Touretzky D S. The role of the hippocampus in solving the morris water maze. Neural Computation 1998; 10: 73-111. [DOI:10.1162/089976698300017908]
41. Rouach N, Glowinski J, Giaume C. Activity-dependent neuronal control of gap-junctional communication in astrocytes. J Cell Biol 2000a; 149: 1513-26. [DOI:10.1083/jcb.149.7.1513]
42. Rouach N, Glowinski J, Giaume C. Activity-dependent neuronal control of gap-junctional communication in astrocytes. The Journal of cell biology 2000b; 149: 1513-1526. [DOI:10.1083/jcb.149.7.1513]
43. Rouach N, Koulakoff A, Abudara V, Willecke K, Giaume C. Astroglial metabolic networks sustain hippocampal synaptic transmission. science 2008; 322: 1551-1555. [DOI:10.1126/science.1164022]
44. Sancho L, Contreras M, Allen N J. Glia as sculptors of synaptic plasticity. Neuroscience Research 2021; 167: 17-29. [DOI:10.1016/j.neures.2020.11.005]
45. Shiosaka S, Yamamoto T, Hertzberg E L, Nagy J I. Gap junction protein in rat hippocampus: correlative light and electron microscope immunohistochemical localization. J Comp Neurol 1989; 281: 282-97. [DOI:10.1002/cne.902810210]
46. Slotnick B M. Fear behavior and passive avoidance deficits in mice with amygdala lesions. Physiology & Behavior 1973; 11: 717-720. [DOI:10.1016/0031-9384(73)90258-8]
47. Snyder J S, Hong N S, McDonald R J, Wojtowicz J M. A role for adult neurogenesis in spatial long-term memory. Neuroscience 2005; 130: 843-52. [DOI:10.1016/j.neuroscience.2004.10.009]
48. Stehberg J, Moraga-Amaro R, Salazar C, Becerra A, Echeverria C, Orellana J A, et al. Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala. Faseb j 2012; 26: 3649-57. [DOI:10.1096/fj.11-198416]
49. Theis M, Giaume C. Connexin-based intercellular communication and astrocyte heterogeneity. Brain research 2012; 1487: 88-98. [DOI:10.1016/j.brainres.2012.06.045]
50. Velazquez J P, Frantseva M, Naus C, Bechberger J, Juneja S, Velumian A, et al. Development of astrocytes and neurons in cultured brain slices from mice lacking connexin43. Developmental brain research 1996; 97: 293-296. [DOI:10.1016/S0165-3806(96)00156-3]
51. Wallraff A, Köhling R, Heinemann U, Theis M, Willecke K, Steinhäuser C. The impact of astrocytic gap junctional coupling on potassium buffering in the hippocampus. Journal of Neuroscience 2006; 26: 5438-5447. [DOI:10.1523/JNEUROSCI.0037-06.2006]
52. Walrave L, Vinken M, Albertini G, De Bundel D, Leybaert L, Smolders I J. Inhibition of connexin43 hemichannels impairs spatial short-term memory without affecting spatial working memory. Frontiers in cellular neuroscience 2016; 10: 288. [DOI:10.3389/fncel.2016.00288]
53. Willecke K, Eiberger J, von Maltzahn J. Connexin and pannexin genes in the mouse and human genome. In: Winterhager E, editor. Gap Junctions in Development and Disease. Berlin, Heidelberg: Springer Berlin Heidelberg, 2005: 1-12. [DOI:10.1007/3-540-28621-7_1]
54. Zhang J, Griemsmann S, Wu Z, Dobrowolski R, Willecke K, Theis M, et al. Connexin43, but not connexin30, contributes to adult neurogenesis in the dentate gyrus. Brain Res Bull 2018; 136: 91-100. [DOI:10.1016/j.brainresbull.2017.07.001]
55. Zhang W, Yin J, Gao B Y, Lu X, Duan Y J, Liu X Y, et al. Inhibition of astroglial hemichannels ameliorates infrasonic noise-induced short-term learning and memory impairment. Behav Brain Funct 2023; 19: 23. [DOI:10.1186/s12993-023-00226-7]

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