Volume 27, Issue 2 (July 2023)                   Physiol Pharmacol 2023, 27(2): 192-201 | Back to browse issues page


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Atabaki-Mehr S, Airian S, Gholami Pourbadie H. Estradiol preserves synapse-related proteins against oligomeric amyloid beta in the hippocampal cultured cells: possible involvement of protein kinase M zeta. Physiol Pharmacol 2023; 27 (2) :192-201
URL: http://ppj.phypha.ir/article-1-1920-en.html
Abstract:   (918 Views)
Introduction: Estradiol has been shown to facilitate synaptic long-term potentiation (LTP) mainly through translocation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor from intracellular pool to the post synaptic membrane. On the other hand, oligomeric amyloid beta (oAβ) decreases number of AMPA receptors in the synapses. It is well known that trafficking of AMPA receptors is governed by an atypical and autonomously active isoform of PKC called protein kinase M zeta (PKMζ). In spite of these evidence, the effect of estradiol on PKMζ expression is not yet studied. We aim to examine the possible protective effect of estradiol on PKMζ and AMPA receptor subunits against oAβ in hippocampal primary cell culture.
Methods: Primary cell culture was prepared from postnatal (P0 to P3) rat pups. They were decapitated and the brains were removed. Hippocampi were isolated and collected in cold phosphate buffer saline. Then, they were trypsinized at 37°C for 15min. The cells were treated with 1µM OAβ or vehicle for 24h and then with 100nM estradiol for another 24h. Using the western blot analysis, the expression level of AMPAR subunit glutamate receptor 1 (GluA1), GluA2 and PKMζ were determined.
Results: OAβ decreased the level of GluA1, GluA2 and PKMζ. Estradiol did not change the molecule levels in healthy cells; however, it preserved their expression levels in OAβ treated cells.
Conclusion: These findings suggest that estradiol may restore expression level of synapse related molecules in an Alzheimer’ disease cell model, in part, through acting on PKMζ signaling pathway.
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References
1. Aliakbari S, Sayyah M, Mirzapourdelavar H, Amini N, Naghdi N, Pourbadie HG. Overexpression of protein kinase Mζ in the hippocampal dentate gyrus rescues amyloid-β-induced synaptic dysfunction within entorhinal-hippocampal circuit. Neurobiol Aging 2021; 101: 160-71. [DOI:10.1016/j.neurobiolaging.2021.01.017]
2. Alzheimer’s Association. 2017 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia 2017; 13: 325-373.
3. Amini N, Azad RR, Motamedi F, Mirzapour-Delavar H, Ghasemi S, Aliakbari S, et al. Overexpression of protein kinase Mζ in the hippocampus mitigates Alzheimer’s disease-related cognitive deficit in rats. Brain Res Bull 2021; 166: 64-72. [DOI:10.1016/j.brainresbull.2020.11.001]
4. Avila JA, Alliger AA, Carvajal B, Zanca RM, Serrano PA, Luine VN. Estradiol rapidly increases GluA2-mushroom spines and decreases GluA2-filopodia spines in hippocampus CA1. Hippocampus 2017; 27: 1224-9. [DOI:10.1002/hipo.22768]
5. Brann DW, Mahesh VB. Excitatory amino acids: function and significance in reproduction and neuroendocrine regulation. Front Neuroendocrinol 1994; 15: 3-49. [DOI:10.1006/frne.1994.1002]
6. Brookmeyer R, Evans DA, Hebert L, Langa KM, Heeringa S G, Plassman BL, et al. National estimates of the prevalence of Alzheimer’s disease in the United States. Alzheimers Dement 2011; 7: 61-73. [DOI:10.1016/j.jalz.2010.11.007]
7. Cantanelli P, Sperduti S, Ciavardelli D, Stuppia L, Gatta V, Sensi SL. Age-dependent modifications of AMPA receptor subunit expression levels and related cognitive effects in 3xTg-AD mice. Front Aging Neurosci 2014; 6: 200. [DOI:10.3389/fnagi.2014.00200]
8. Carter CL, Resnick EM, Mallampalli M, Kalbarczyk A. Sex and gender differences in Alzheimer’s disease: recommendations for future research. J Womens Health (Larchmt) 2012; 21: 1018-23. [DOI:10.1089/jwh.2012.3789]
9. Evin G, Weidemann A. Biogenesis and metabolism of Alzheimer’s disease Aβ amyloid peptides. Peptides 2002; 23: 1285-97. [DOI:10.1016/S0196-9781(02)00063-3]
10. Ferri S L, Hildebrand P F, Way S E, Flanagan-Cato L M. Estradiol regulates markers of synaptic plasticity in the hypothalamic ventromedial nucleus and amygdala of female rats. Horm Behav . 2014; 66: 409-420. [DOI:10.1016/j.yhbeh.2014.06.016]
11. Foy MR, Xu J, Xie X, Brinton RD, Thompson RF, Berger TW. 17beta-estradiol enhances NMDA receptor-mediated EPSPs and long-term potentiation. J Neurophysiol 1999; 81: 925-9. [DOI:10.1152/jn.1999.81.2.925]
12. Fugger HN, Kumar A, Lubahn DB, Korach KS, Foster TC. Examination of estradiol effects on the rapid estradiol mediated increase in hippocampal synaptic transmission in estrogen receptor α knockout mice. Neurosci Lett 2001; 309: 207-9. [DOI:10.1016/S0304-3940(01)02083-3]
13. Guntupalli S, Widagdo J, Anggono V. Amyloid-β-induced dysregulation of AMPA receptor trafficking. Neural Plast 2016; 2016: 3204519. [DOI:10.1155/2016/3204519]
14. Hasegawa Y, Hojo Y, Kojima H, Ikeda M, Hotta K, Sato R, et al. Estradiol rapidly modulates synaptic plasticity of hippocampal neurons: involvement of kinase networks. Brain Res 2015; 1621: 147-61. [DOI:10.1016/j.brainres.2014.12.056]
15. Heshmati-Fakhr N, Sotoodehnejadnematalahi F, Yousefi N, Sayyah M, Hosseini SM, Pourbadie HG. Triggering microglia through toll-like receptor 2 pathway induced interferon β expression in cell and animal model of Alzheimer’s disease. Neuroreport 2018; 29: 1456-62. [DOI:10.1097/WNR.0000000000001132]
16. Irvine K, Laws KR, Gale TM, Kondel TK. Greater cognitive deterioration in women than men with Alzheimer’s disease: a meta analysis. J Clin Exp Neuropsychol 2012; 34: 989-98. [DOI:10.1080/13803395.2012.712676]
17. Kajta M, Budziszewska B, Marszal M, Lason W. Effects of 17-beta estradiol and estriol on NMDA-induced toxicity and apoptosis in primary cultures of rat cortical neurons. J Physiol Pharmacol. 2001; 52: 437-46
18. Konen LM, Wright AL, Royle GA, Morris GP, Lau BK, Seow PW, et al. A new mouse line with reduced GluA2 Q/R site RNA editing exhibits loss of dendritic spines, hippocampal CA1-neuron loss, learning and memory impairments and NMDA receptor-independent seizure vulnerability. Mol Brain 2020; 13: 1-19. [DOI:10.1186/s13041-020-0545-1]
19. Koss W, Frick KM. Activation of androgen receptors protects intact male mice from memory impairments caused by aromatase inhibition. Horm Behav 2019; 111:96-104. [DOI:10.1016/j.yhbeh.2019.01.002]
20. Kramár EA, Babayan AH, Gall CM, Lynch G. Estrogen promotes learning-related plasticity by modifying the synaptic cytoskeleton. Neuroscience 2013; 239: 3-16. [DOI:10.1016/j.neuroscience.2012.10.038]
21. Ling DSF, Benardo LS, Serrano PA, Blace N, Kelly MT, Crary JF, et al. Protein kinase Mζ is necessary and sufficient for LTP maintenance. Nat Neurosci 2002; 5: 295-6. [DOI:10.1038/nn829]
22. Liu SJ, Gasperini R, Foa L, Small DH. Amyloid-beta decreases cell-surface AMPA receptors by increasing intracellular calcium and phosphorylation of GluR2. J Alzheimers Dis 2010; 21: 655-66. [DOI:10.3233/JAD-2010-091654]
23. Lu W, Shi Y, Jackson A C, Bjorgan K, During MJ, Sprengel R, et al. Subunit composition of synaptic AMPA receptors revealed by a single-cell genetic approach. Neuron 2009; 62: 254-68. [DOI:10.1016/j.neuron.2009.02.027]
24. Lüthi A, Chittajallu R, Duprat F, Palmer MJ, Benke TA, Kidd FL, et al. Hippocampal LTD expression involves a pool of AMPARs regulated by the NSF-GluR2 interaction. Neuron 1999; 24: 389-99. [DOI:10.1016/S0896-6273(00)80852-1]
25. Miñano-Molina AJ, España J, Martín E, Barneda-Zahonero B, Fadó R, Solé M, et al. Soluble oligomers of amyloid-β peptide disrupt membrane trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor contributing to early synapse dysfunction. J Biol Chem 2011; 286: 27311-21. [DOI:10.1074/jbc.M111.227504]
26. Pagliusi SR, Gerrard P, Abdallah M, Talabot D, Catsicas S. Age-related changes in expression of AMPA-selective glutamate receptor subunits: is calcium-permeability altered in hippocampal neurons? Neuroscience 1994; 61: 429-33. [DOI:10.1016/0306-4522(94)90422-7]
27. Plant K, Pelkey KA, Bortolotto Z A, Morita D, Terashima A, McBain CJ, et al. Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation. Nat Neurosci 2006; 9: 602-4. [DOI:10.1038/nn1678]
28. Pourbadie HG, Naderi N, Janahmadi M, Mehranfard N, Motamedi F. Calcium channel blockade attenuates abnormal synaptic transmission in the dentate gyrus elicited by entorhinal amyloidopathy. Synapse 2016; 70: 408-17. [DOI:10.1002/syn.21915]
29. Pourbadie HG, Naderi N, Mehranfard N, Janahmadi M, Khodagholi F, Motamedi F. Preventing effect of L-type calcium channel blockade on electrophysiological alterations in dentate gyrus granule cells induced by entorhinal amyloid pathology. Plos one 2015; 10: e0117555. [DOI:10.1371/journal.pone.0117555]
30. Pourbadie HG, Sayyah M, Khoshkholgh-Sima B, Choopani S, Nategh M, Motamedi F, et al. Early minor stimulation of microglial TLR2 and TLR4 receptors attenuates Alzheimer’s disease-related cognitive deficit in rats: behavioral, molecular, and electrophysiological evidence. Neurobiol Aging 2018; 70: 203-16. [DOI:10.1016/j.neurobiolaging.2018.06.020]
31. Resende R, Pereira C, Agostinho P, Vieira A, Malva JO, Oliveira CR. Susceptibility of hippocampal neurons to Aβ peptide toxicity is associated with perturbation of Ca2+ homeostasis. Brain Res 2007; 1143: 11-21. [DOI:10.1016/j.brainres.2007.01.071]
32. Rui Y, Gu J, Yu K, Hartzell HC, Zheng JQ. Inhibition of AMPA receptor trafficking at hippocampal synapses by β-amyloid oligomers: the mitochondrial contribution. Mol Brain 2010; 3: 1-13. [DOI:10.1186/1756-6606-3-10]
33. Schuette SR, Fernández-Fernández D, Lamla T, Rosenbrock H, Hobson S. Overexpression of protein kinase Mζ in the hippocampus enhances long-term potentiation and long-term contextual but not cued fear memory in rats. J Neurosci 2016; 36: 4313-24. [DOI:10.1523/JNEUROSCI.3600-15.2016]
34. Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 2016; 8: 595-608. [DOI:10.15252/emmm.201606210]
35. Selkoe DJ, Podlisny MB. Deciphering the genetic basis of Alzheimer’s disease. Annu Rev Genomics Hum Genet 2002; 3: 67-99. [DOI:10.1146/annurev.genom.3.022502.103022]
36. Sengupta U, Nilson AN, Kayed R. The role of amyloid-β oligomers in toxicity, propagation, and immunotherapy. EBioMedicine 2016; 6: 42-9. [DOI:10.1016/j.ebiom.2016.03.035]
37. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, et al. Amyloid-β protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 2008; 14: 837-42. [DOI:10.1038/nm1782]
38. Shao CY, Sondhi R, van de Nes PS, Sacktor TC. PKMζ is necessary and sufficient for synaptic clustering of PSD-95. Hippocampus 2012; 22: 1501-7. [DOI:10.1002/hipo.20996]
39. Shema R, Sacktor TC, Dudai Y. Rapid erasure of long-term memory associations in the cortex by an inhibitor of PKM zeta. Science 2007; 317: 951-3. [DOI:10.1126/science.1144334]
40. Smith CC, McMahon L. Estrogen-induced increase in the magnitude of long-term potentiation occurs only when the ratio of NMDA transmission to AMPA transmission is increased. J Neurosci 2005; 25: 7780-91. [DOI:10.1523/JNEUROSCI.0762-05.2005]
41. Uddin MS, Rahman MM, Jakaria M, Rahman MS, Hossain MS, Islam A, et al. Estrogen signaling in Alzheimer’s disease: molecular insights and therapeutic targets for Alzheimer’s dementia. Mol Neurobiol 2020; 57: 2654-70. [DOI:10.1007/s12035-020-01911-8]
42. Valian N, Heravi M, Ahmadiani A, Dargahi L. Comparison of Rat Primary Midbrain Neurons Cultured in DMEM/F12 and Neurobasal Mediums. asic Clin Neurosci. 2021 Mar-Apr; 12: 205–212. https://doi.org/ 10.32598/bcn.12.2.1568.1 [DOI:10.32598/bcn.12.2.1568.1]
43. Yao Y, Kelly MT, Sajikumar S, Serrano P, Tian D, Bergold PJ, et al. PKM zeta maintains late long-term potentiation by N-ethylmaleimide-sensitive factor/GluR2-dependent trafficking of postsynaptic AMPA receptors. J Neurosci 2008; 28: 7820-7. [DOI:10.1523/JNEUROSCI.0223-08.2008]
44. Yousefi N, Sotoodehnejadnematalahi F, Heshmati-Fakhr N, Sayyah M, Hoseini M, Ghassemi S, et al. Prestimulation of microglia through TLR4 pathway promotes interferon beta expression in a rat model of Alzheimer’s disease. J Mol Neurosci 2019; 67: 495-503. [DOI:10.1007/s12031-018-1249-1]
45. Zadran S, Qin Q, Bi X, Zadran H, Kim Y, Foy MR, et al. 17-Beta- estradiol increases neuronal excitability through MAP kinase-induced calpain activation. PNAS 2009; 106: 21936-41. [DOI:10.1073/pnas.0912558106]
46. Zandi P P, Carlson M C, Plassman B L, Welsh-Bohmer K A, Mayer L S, Steffens D C, et al. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study. JAMA 2002; 288: 2123-2129. [DOI:10.1001/jama.288.17.2123]
47. Zhang Y, Guo O, Huo Y, Wang G, Man HY. Amyloid-β induces AMPA receptor ubiquitination and degradation in primary neurons and human brains of Alzheimer’s disease. J Alzheimers Dis 2018; 62: 1789-801. [DOI:10.3233/JAD-170879]
48. Zhao WQ, Santini F, Breese R, Ross D, Zhang XD, Stone DJ, et al. Inhibition of calcineurin-mediated endocytosis and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors prevents amyloid β oligomer-induced synaptic disruption. J Biol Chem 2010; 285: 7619-32. [DOI:10.1074/jbc.M109.057182]

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