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Kainate-Induced Degeneration of Hippocampal Neurons. Protective Effect of Activation of the Endocannabinoid System

  • BIOPHYSICS AND BIOCHEMISTRY
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Bulletin of Experimental Biology and Medicine Aims and scope

We studied the prolonged action of kainic acid on glutamatergic neurons in the dorsal hippocampus and the endocannabinoid-dependent protection against neurodegeneration. The pyramidal neurons of the CA3 field of the hippocampus, as well as granular and mossy cells of the dentate gyrus were examined. Light and electron microscopy revealed substantial damage to the components of the protein-synthesizing (rough endoplasmic reticulum, Golgi apparatus, and polyribosomes) and catabolic (lysosomes, autophagosomes, multivesicular structures, and lipofuscin formations) systems in all cells. Pyramidal and mossy neurons die mainly by the necrotic pathway. The death of granular cells occurred through both apoptosis and necrosis. The most vulnerable cells are mossy neurons located in the hilus. Activation of the endocannabinoid system induced by intracerebral injection of URB597, an inhibitor of degradation of endocannabinoid anandamide, protected the normal structure of the hippocampus and prevented neuronal damage and death induced by KA.

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References

  1. Campbell VA, Downer EJ. Cannabinoids and neuroprotection. Cannabinoids and the Brain. Köfalvi A, ed. Boston, 2008. P. 317-329.

  2. Chen C, Qin H, Tan J, Hu Z, Zeng L. The role of ubiquitinproteasome pathway and autophagy lysosome pathway in cere bral ischemia. Oxid. Med. Cell. Longev. 2020;2020:5457049. doi: https://doi.org/10.1155/2020/5457049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Karanian DA, Karim SL, Wood JT, Williams JS, Lin S, Makriyannis A, Bahr BA. Endocannabinoid enhancement protects against kainic acid-induced seizures and associated brain damage. J. Pharmacol. Exp. Ther. 2007;322(3):1059-1066. doi: https://doi.org/10.1124/jpet.107.120147

    Article  CAS  PubMed  Google Scholar 

  4. Kron MM, Zhang H, Parent JM. The developmental stage of dentate granule cells dictates their contribution to seizureinduced plasticity. J. Neurosci. 2010;30(6):2051-2059. doi: https://doi.org/10.1523/JNEUROSCI.5655-09.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lupica CR, Hu Y, Devinsky O, Hoffman AF. Cannabinoids as hippocampal network administrators. Neuropharmacol. 2017;124:25-37. doi: https://doi.org/10.1016/j.neuropharm.2017.04.003

    Article  CAS  Google Scholar 

  6. Méndez-Armenta M, Nava-Ruíz C, Juárez-Rebollar D, Rodríguez-Martínez E, Gómez PY. Oxidative stress asso ciated with neuronal apoptosis in experimental models of epilepsy. Oxid. Med. Cell. Longev. 2014;2014:293689. doi: https://doi.org/10.1155/2014/293689

    Article  PubMed  PubMed Central  Google Scholar 

  7. Monory K, Massa F, Egertová M, Eder M, Blaudzun H, Westenbroek R, Kelsch W, Jacob W, Marsch R, Ekker M, Long J, Rubenstein JL, Goebbels S, Nave KA, During M, Klugmann M, Wölfel B, Dodt HU, Zieglgänsberger W, Wotjak CT, Mackie K, Elphick MR, Marsicano G, Lutz B. The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron. 2006;51(4):455-466. doi: https://doi.org/10.1016/j.neuron.2006.07.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. Sydney, 1998.

    Google Scholar 

  9. Scharfman HE. Advances in understanding hilar mossy cells of the dentate gyrus. Cell Tissue Res. 2018;373(3):643-652. doi: https://doi.org/10.1007/s00441-017-2750-5

    Article  CAS  PubMed  Google Scholar 

  10. Sulzer D, Mosharov E, Talloczy Z, Zucca FA, Simon JD, Zecca L. Neuronal pigmented autophagic vacuoles: lipofuscin, neuromelanin, and ceroid as macroautophagic responses during aging and disease. J. Neurochem. 2008;106(1):24-36. doi: https://doi.org/10.1111/j.1471-4159.2008.05385.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Thodeson DM, Brulet R, Hsieh J. Neural stem cells and epilepsy: functional roles and disease-in-a-dish models. Cell Tissue Res. 2018;371(1):47-54. doi: https://doi.org/10.1007/s00441-017-2675-z

    Article  PubMed  Google Scholar 

  12. Vincent P, Mulle C. Kainate receptors in epilepsy and excitotoxicity. Neuroscience. 2009;158(1):309-323. doi: https://doi.org/10.1016/j.neuroscience.2008.02.066

    Article  CAS  PubMed  Google Scholar 

  13. Yuan Y, Wang H, Wei Z, Li W. Impaired autophagy in hilar mossy cells of the dentate gyrus and its implication in schizophrenia. J. Genet. Genomics. 2015;42(1):1-8. doi: https://doi.org/10.1016/j.jgg.2014.12.001

    Article  CAS  PubMed  Google Scholar 

  14. Zheng XY, Zhang HL, Luo Q, Zhu J. Kainic acid-induced neurodegenerative model: potentials and limitations. J. Biomed. Biotechnol. 2011;2011:457079. doi: https://doi.org/10.1155/2011/457079

    Article  CAS  PubMed  Google Scholar 

  15. Zhou H, Chen L, Gao X, Luo B, Chen J. Moderate traumatic brain injury triggers rapid necrotic death of immature neurons in the hippocampus. J. Neuropathol. Exp. Neurol. 2012;71(4):348-359. doi: https://doi.org/10.1097/NEN.0b013e31824ea078

    Article  PubMed  Google Scholar 

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Correspondence to R. Ya. Gordon.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 171, No. 3, pp. 307-312, March, 2021

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Gordon, R.Y., Mikheeva, I.B., Shubina, L.V. et al. Kainate-Induced Degeneration of Hippocampal Neurons. Protective Effect of Activation of the Endocannabinoid System. Bull Exp Biol Med 171, 327–332 (2021). https://doi.org/10.1007/s10517-021-05221-4

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  • DOI: https://doi.org/10.1007/s10517-021-05221-4

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