Comparative investigation of glutamate and GABA gene expression in the hippocampus after focal brain ischemia and central lps administration

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Abstract

Among the responses in the early stages of stroke, activation of neurodegenerative and proinflammatory processes in the hippocampus is of key importance for the development of negative post-ischemic functional consequences. However, it remains unclear which genes are involved in these processes. The aim of this work was a comparative study of the expression of genes encoding glutamate and GABA transporters and receptors, as well as inflammation markers in the hippocampus one day after two types of ischemic exposure (according to Koizumi - MCAO-MK, and Longa - MCAO-ML), as well as after direct pro-inflammatory activation by central administration of lipopolysaccharide (LPS). The results obtained revealed both differences and similarities between the responses to the impacts applied in the work. A greater number of genes that changed the expression associated with the activation of apoptosis and neuroinflammation, glutamate reception, and markers of the GABAergic system were found after MCAO-ML and LPS, than after MCAO-MK. In turn, MCAO-MK and LPS were characterized, in comparison with MCAO-ML, by changes in a larger number of genes involved in glutamate transport. The most pronounced difference between MCAO-ML and MCAO-MK and LPS was changes in the expression of genes for calmodulin and calmodulin-dependent kinases. The revealed features of the responses of the hippocampal transcriptome to two types of ischemia and a pro-inflammatory stimulus will contribute to further understanding of the causes of the diversity of stroke consequences, both in model studies and in the clinic.

About the authors

T. S Kalinina

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Email: gtshi@bionet.nsc.ru
630090 Novosibirsk, Russia

G. T Shishkina

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Email: gtshi@bionet.nsc.ru
630090 Novosibirsk, Russia

D. A Lanshakov

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Email: gtshi@bionet.nsc.ru
630090 Novosibirsk, Russia

E. V Sukhareva

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Email: gtshi@bionet.nsc.ru
630090 Novosibirsk, Russia

M. V Onufriev

Institute of Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences

Email: gtshi@bionet.nsc.ru
117485 Moscow, Russia

Y. V Moiseeva

Institute of Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences

Email: gtshi@bionet.nsc.ru
117485 Moscow, Russia

N. V Gulyaeva

Institute of Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences

Email: gtshi@bionet.nsc.ru
117485 Moscow, Russia

N. N Dygalo

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Email: gtshi@bionet.nsc.ru
630090 Novosibirsk, Russia

References

  1. Rudolph, M., Schmeer, C. W., Günther, M., Woitke, F., Kathner-Schaffert, C., Karapetow, L., Lindner, J., Lehmann, T., Jirikowski, G., Witte, O. W., Redecker, C., and Keiner, S. (2021) Microglia-mediated phagocytosis of apoptotic nuclei is impaired in the adult murine hippocampus after stroke, Glia, 69, 2006-2022, doi: 10.1002/glia.24009.
  2. Rolls, E. T. (1996) A theory of hippocampal function in memory, Hippocampus, 6, 601-620, doi: 10.1002/(SICI)1098-1063(1996)6:6<601::AID-HIPO5>3.0.CO;2-J.
  3. Gulyaeva, N. V., Onufriev, M. V., and Moiseeva, Y. V. (2021) Ischemic stroke, glucocorticoids, and remote hippocampal damage: a translational outlook and implications for modeling, Front. Neurosci., 15, 781964, doi: 10.3389/fnins.2021.781964.
  4. Robinson, R. G., and Jorge, R. E. (2016) Post-stroke depression: a review, Am. J. Psychiatry, 173, 221-231, doi: 10.1176/appi.ajp.2015.15030363.
  5. Globus, M. Y., Busto, R., Martinez, E., Valdes, I., Dietrich, W. D., and Ginsberg, M. D. (1991) Comparative effect of transient global ischemia on extracellular levels of glutamate, glycine, and gamma-aminobutyric acid in vulnerable and nonvulnerable brain regions in the rat, J. Neurochem., 57, 470-478, doi: 10.1111/j.1471-4159.1991.tb03775.x.
  6. Luo, Y., Ma, H., Zhou, J. J., Li, L., Chen, S. R., Zhang, J., Chen, L., and Pan, H. L. (2018) Focal cerebral ischemia and reperfusion induce brain injury through α2δ-1-bound NMDA receptors, Stroke, 49, 2464-2472, doi: 10.1161/STROKEAHA.118.022330.
  7. Magi, S., Piccirillo, S., and Amoroso, S. (2019) The dual face of glutamate: from a neurotoxin to a potential survival factor-metabolic implications in health and disease, Cell. Mol. Life Sci., 76, 1473-1488, doi: 10.1007/s00018-018-3002-x.
  8. Deisseroth, K., Singla, S., Toda, H., Monje, M., Palmer, T. D., and Malenka, R. C. (2004) Excitation-neurogenesis coupling in adult neural stem/progenitor cells, Neuron, 42, 535-552, doi: 10.1016/s0896-6273(04)00266-1.
  9. Hu, J., Li, C., Hua, Y., Liu, P., Gao, B., Wang, Y., and Bai, Y. (2020) Constraint-induced movement therapy improves functional recovery after ischemic stroke and its impacts on synaptic plasticity in sensorimotor cortex and hippocampus, Brain Res. Bull., 160, 8-23, doi: 10.1016/j.brainresbull.2020.04.006.
  10. Ikonomidou, C., and Turski, L. (2002) Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol., 1, 383-386, doi: 10.1016/s1474-4422(02)00164-3.
  11. Biegon, A., Liraz-Zaltsman, S., and Shohami, E. (2018) Stimulation of N-methyl-D-aspartate receptors by exogenous and endogenous ligands improves outcome of brain injury, Curr. Opin. Neurol., 31, 687-692, doi: 10.1097/WCO.0000000000000612.
  12. Shishkina, G. T., Kalinina, T. S., Gulyaeva, N. V., Lanshakov, D. A., and Dygalo, N. N. (2021) Changes in gene expression and neuroinflammation in the hippocampus after focal brain ischemia: involvement in the long-term cognitive and mental disorders, Biochemistry (Moscow), 86, 657-666, doi: 10.1134/S0006297921060043.
  13. Batista, C. R. A., Gomes, G. F., Candelario-Jalil, E., Fiebich, B. L., and de Oliveira, A. C. P. (2019) Lipopolysaccharide-induced neuroinflammation as a bridge to understand neurodegeneration, Int. J. Mol. Sci., 20, 2293, doi: 10.3390/ijms20092293.
  14. Chung, J. Y., Yi, J. W., Kim, S. M., Lim, Y. J., Chung, J. H., and Jo, D. J. (2011) Changes in gene expression in the rat hippocampus after focal cerebral ischemia, J. Korean Neurosurg. Soc., 50, 173-178, doi: 10.3340/jkns.2011.50.3.173.
  15. Wang, C., Liu, M., Pan, Y., Bai, B., and Chen, J. (2017) Global gene expression profile of cerebral ischemia-reperfusion injury in rat MCAO model, Oncotarget, 8, 74607-74622, doi: 10.18632/oncotarget.20253.
  16. Shishkina, G. T., Gulyaeva, N. V., Lanshakov, D. A., Kalinina, T. S., Onufriev, M. V., Moiseeva, Y. V., Sukhareva, E. V., and Babenko, V. N. (2021) Identifying the involvement of pro-inflammatory signal in hippocampal gene expression changes after experimental ischemia: transcriptome-wide analysis, Biomedicines, 9, 1840, doi: 10.3390/biomedicines9121840.
  17. Bonow, R. H., Aïd, S., Zhang, Y., Becker, K. G., and Bosetti, F. (2009) The brain expression of genes involved in inflammatory response, the ribosome, and learning and memory is altered by centrally injected lipopolysaccharide in mice, Pharmacogenomics J., 9, 116-126, doi: 10.1038/tpj.2008.15.
  18. Smith, H. K., Russell, J. M., Granger, D. N., and Gavins, F. N. (2015) Critical differences between two classical surgical approaches for middle cerebral artery occlusion-induced stroke in mice, J. Neurosci. Methods, 249, 99-105, doi: 10.1016/j.jneumeth.2015.04.008.
  19. Shah, F. A., Li, T., Kury, L. T. A., Zeb, A., Khatoon, S., Liu, G., Yang, X., Liu, F., Yao, H., Khan, A.-U., Koh, P. O., Jiang, Y., and Li, S. (2019) Pathological comparisons of the hippocampal changes in the transient and permanent middle cerebral artery occlusion rat models, Front. Neurol., 10, 1178, doi: 10.3389/fneur.2019.01178.
  20. Onufriev, M. V., Moiseeva, Y. V., Zhanina, M. Y., Lazareva, N. A., and Gulyaeva, N. V. (2021) A comparative study of Koizumi and Longa methods of intraluminal filament middle cerebral artery occlusion in rats: early corticosterone and inflammatory response in the hippocampus and frontal cortex, Int. J. Mol. Sci., 22, 13544, doi: 10.3390/ijms222413544.
  21. Koizumi, J.Y., Nakazawa, T., and Ooneda, G. (1986) Experimental studies of ischemic cerebral edema. I. A new experimental model of cerebral embolism in rats in which recirculation in the ischemic area can be introduced, Jpn. J. Stroke, 8, 1-8, doi: 10.3995/jstroke.8.1.
  22. Longa, E. Z., Weinstein, P. R., Carlson, S., and Cummins, R. (1989) Reversible middle cerebral artery occlusion without craniectomy in rats, Stroke, 20, 84-91, doi: 10.1161/01.str.20.1.84.
  23. Onufriev, M. V., Stepanichev, M. Y., Moiseeva, Y. V., Zhanina, M. Y., Nedogreeva, O. A., Kostryukov, P. A., Lazareva, N. A., and Gulyaeva, N. V. (2022) A comparative study of two models of intraluminal filament middle cerebral artery occlusion in rats: long lasting accumulation of corticosterone and interleukins in the hippocampus and frontal cortex in Koizumi model, Biomedicines, 10, 3119, doi: 10.3390/biomedicines10123119.
  24. Arvidsson, A., Kokaia, Z., and Lindvall, O. (2001) N-methyl-D-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke, Eur. J. Neurosci., 14, 10-18, doi: 10.1046/j.0953-816x.2001.01611.x.
  25. Dygalo, N. N., Bannova, A. V., Kalinina, T. S., and Shishkina, G. T. (2004) Clonidine increases caspase-3 mRNA level and DNA fragmentation in the developing rat brainstem, Dev. Brain Res., 152, 225-231, doi: 10.1016/j.devbrainres.2004.06.018.
  26. Gulyaeva, N. V. (2019) Biochemical mechanisms and translational relevance of hippocampal vulnerability to distant focal brain injury: the price of stress response, Biochemistry (Moscow), 84, 1306-1328, doi: 10.1134/S0006297919110087.
  27. Gulyaeva, N. V. (2019) Functional neurochemistry of the ventral and dorsal hippocampus: stress, depression, dementia and remote hippocampal damage, Neurochem. Res., 44, 1306-1322, doi: 10.1007/s11064-018-2662-0.
  28. Li, Y., Tan, L., Yang, C., He, L., Deng, B., Huang, X., Liu, S., Liu, L., Wang, J., and Guo, J. (2022) Comparison of middle cerebral artery occlusion models conducted by Koizumi and Longa methods: a systematic review and meta-analysis of rodent data [Preprint], Research Square, doi: 10.21203/rs.3.rs-2398116/v1.
  29. Gulyaeva, N., Thompson, C., Shinohara, N., Lazareva, N., Onufriev, M., Stepanichev, M., Moiseeva, Y., Fliss, H., and Hakim, A. M. (2003) Tongue protrusion: a simple test for neurological recovery in rats following focal cerebral ischemia, J. Neurosci. Methods, 125, 183-193, doi: 10.1016/s0165-0270(03)00056-6.
  30. Zhanina, M. Y., Druzhkova, T. A., Yakovlev, A. A., Vladimirova, E. E., Freiman, S. V., Eremina, N. N., Guekht, A. B., and Gulyaeva, N. V. (2022) Development of post-stroke cognitive and depressive disturbances: associations with neurohumoral indices, Curr. Issues Mol. Biol., 44, 6290-6305, doi: 10.3390/cimb44120429.
  31. States, B. A., Honkaniemi, J., Weinstein, P. R., and Sharp, F. R. (1996) DNA fragmentation and HSP70 protein induction in hippocampus and cortex occurs in separate neurons following permanent middle cerebral artery occlusions, J. Cereb. Blood Flow Metab., 16, 1165-1175, doi: 10.1097/00004647-199611000-00011.
  32. Uchida, H., Fujita, Y., Matsueda, M., Umeda, M., Matsuda, S., Kato, H., Kasahara, J., Araki, T. (2010) Damage to neurons and oligodendrocytes in the hippocampal CA1 sector after transient focal ischemia in rats, Cell. Mol. Neurobiol., 30, 1125-1134, doi: 10.1007/s10571-010-9545-5.
  33. Ransohoff, R. M. (2016) How neuroinflammation contributes to neurodegeneration, Science, 353, 777-783, doi: 10.1126/science.aag2590.
  34. Xu, A. L., Zheng, G. Y., Ye, H. Y., Chen, X. D., and Jiang, Q. (2020) Characterization of astrocytes and microglial cells in the hippocampal CA1 region after transient focal cerebral ischemia in rats treated with Ilexonin A, Neural Regen. Res., 15, 78-85, doi: 10.4103/1673-5374.264465.
  35. Rosenberg, G. A. (2009) Matrix metalloproteinases and their multiple roles in neurodegenerative diseases, Lancet Neurol., 8, 205-216, doi: 10.1016/S1474-4422(09)70016-X.
  36. Hannocks, M. J., Zhang, X., Gerwien, H., Chashchina, A., Burmeister, M., Korpos, E., Song, J., and Sorokin, L. (2019) The gelatinases, MMP-2 and MMP-9, as fine tuners of neuroinflammatory processes, Matrix Biol., 75-76, 102-113, doi: 10.1016/j.matbio.2017.11.007.
  37. Liu, Y., Wong, T. P., Aarts, M., Rooyakkers, A., Liu, L., Lai, T. W., Wu, D. C., Lu, J., Tymianski, M., Craig, A. M., and Wang, Y. T. (2007) NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo, J. Neurosci., 27, 2846-2857, doi: 10.1523/JNEUROSCI.0116-07.2007.
  38. Szydlowska, K., and Tymianski, M. (2010) Calcium, ischemia and excitotoxicity, Cell Calcium, 47, 122-129, doi: 10.1016/j.ceca.2010.01.003.
  39. Kalia, L. V., Kalia, S. K., and Salter, M. W. (2008) NMDA receptors in clinical neurology: excitatory times ahead, Lancet Neurol., 7, 742-755, doi: 10.1016/S1474-4422(08)70165-0.
  40. Yang, Y., Li, Q., Miyashita, H., Yang, T., and Shuaib, A. (2001) Different dynamic patterns of extracellular glutamate release in rat hippocampus after permanent or 30-min transient cerebral ischemia and histological correlation, Neuropathology, 21, 181-187, doi: 10.1046/j.1440-1789.2001.00397.x.
  41. Krzyżanowska, W., Pomierny, B., Bystrowska, B., Pomierny-Chamioło, L., Filip, M., Budziszewska, B., and Pera, J. (2017) Ceftriaxone- and N-acetylcysteine-induced brain tolerance to ischemia: influence on glutamate levels in focal cerebral ischemia, PLoS One, 12, e0186243, doi: 10.1371/journal.pone.0186243.
  42. Magi, S., Piccirillo, S., Amoroso, S., and Lariccia, V. (2019) Excitatory amino acid transporters (EAATs): glutamate transport and beyond, Int. J. Mol. Sci., 20, 5674, doi: 10.3390/ijms20225674.
  43. Jiang, T., Jiao, J., Shang, J., Bi, L., Wang, H., Zhang, C., Wu, H., Cui, Y., Wang, P., and Liu, X. (2022) The differences of metabolites in different parts of the brain induced by Shuxuetong Injection against cerebral ischemia-reperfusion and its corresponding mechanism, Evid. Based Complement. Alternat. Med., 2022, 9465095, doi: 10.1155/2022/9465095.
  44. Pocock, J. M., and Kettenmann, H. (2007) Neurotransmitter receptors on microglia, Trends Neurosci., 30, 527-535, doi: 10.1016/j.tins.2007.07.007.
  45. Lori, A., Schultebraucks, K., Galatzer-Levy, I., Daskalakis, N. P., Katrinli, S., Smith, A. K., Myers, A. J., Richholt, R., Huentelman, M., Guffanti, G., Wuchty, S., Gould, F., Harvey, P. D., Nemeroff, C. B., Jovanovic, T., Gerasimov, E. S., Maples-Keller, J. L., Stevens, J. S., Michopoulos, V., Rothbaum, B. O., Wingo, A. P., and Ressler, K. J. (2021) Transcriptome-wide association study of post-trauma symptom trajectories identified GRIN3B as a potential biomarker for PTSD development, Neuropsychopharmacology, 46, 1811-1820, doi: 10.1038/s41386-021-01073-8.
  46. Andersson, O., Stenqvist, A., Attersand, A., and von Euler, G. (2001) Nucleotide sequence, genomic organization, and chromosomal localization of genes encoding the human NMDA receptor subunits NR3A and NR3B, Genomics, 78, 178-184, doi: 10.1006/geno.2001.6666.
  47. Chatterton, J. E., Awobuluyi, M., Premkumar, L. S., Takahashi, H., Talantova, M., Shin, Y., Cui, J., Tu, S., Sevarino, K. A., Nakanishi, N., Tong, G., Lipton, S. A., and Zhang, D. (2002) Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits, Nature, 415, 793-798, doi: 10.1038/nature715.
  48. Mastroiacovo, F., Moyanova, S., Cannella, M., Gaglione, A., Verhaeghe, R., Bozza, G., Madonna, M., Motolese, M., Traficante, A., Riozzi, B., Bruno, V., Battaglia, G., Lodge, D., and Nicoletti, F. (2017) Genetic deletion of mGlu2 metabotropic glutamate receptors improves the short-term outcome of cerebral transient focal ischemia, Mol. Brain, 10, 39, doi: 10.1186/s13041-017-0319-6.
  49. Gulyaeva, N. V. (2021) Glucocorticoid regulation of the glutamatergic synapse: mechanisms of stress-dependent neuroplasticity, J. Evol. Biochem. Physiol., 57, 564-576, doi: 10.1134/S0022093021030091.
  50. Gulyaeva, N. V. (2022) Neuroendocrine control of hyperglutamatergic states in brain pathologies: the effects of glucocorticoids, J. Evol. Biochem. Physiol., 58, 1425-1438, doi: 10.1134/S0022093022050131.
  51. Neumann, S., Boothman-Burrell, L., Gowing, E. K., Jacobsen, T. A., Ahring, P. K., Young, S. L., Sandager-Nielsen, K., and Clarkson, A. N. (2019) The delta-subunit selective GABA a receptor modulator, DS2, improves stroke recovery via an anti-inflammatory mechanism, Front. Neurosci., 13, 1133, doi: 10.3389/fnins.2019.01133.
  52. Hoque, A., Hossain, M. I., Ameen, S. S., Ang, C. S., Williamson, N., Ng, D. C. H., Chueh, A. C., Roulston, C., and Cheng, H.-C. (2016) A beacon of hope in stroke therapy-Blockade of pathologically activated cellular events in excitotoxic neuronal death as potential neuroprotective strategies, Pharmacol. Ther., 160, 159-179, doi: 10.1016/j.pharmthera.2016.02.009.
  53. Balakrishnan, K., Hleihil, M., Bhat, M. A., Ganley, R. P., Vaas, M., Klohs, J., Zeilhofer, H. U., and Benke, D. (2022) Targeting the interaction of GABAB receptors with CaMKII with an interfering peptide restores receptor expression after cerebral ischemia and inhibits progressive neuronal death in mouse brain cells and slices, Brain Pathol., 33, e13099, doi: 10.1111/bpa.13099.

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