Skip to main content
SpringerLink
Log in

Effect of Pharmacological Modulation of Activity of Metabotropic Glutamate Receptors on Their Gene Expression after Excitotoxic Damage in Hippocampal Neurons

  • GENETICS
  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

Microinjection of kainic acid into rat hippocampus causes excitotoxic neuronal damage predominantly in the CA3 and CA1 fields. These lesions can be significantly reduced by simultaneous administration of MPEP, a negative allosteric modulator of type 5 metabotropic glutamate receptors, and LY354740, an agonist of type 2 metabotropic glutamate receptors. The decrease in neuronal death in the hippocampus during pharmacological modulation was paralleled by adaptive changes in gene expression. In the hippocampus, gene expression of type 5 postsynaptic metabotropic glutamate receptor was close to the control level, and in the frontal cortex expression of the gene of α1-subunit of the GABAA receptor returned to normal. In the frontal cortex, a reciprocal relationship was observed for type 2 metabotropic glutamate receptor: expression of the corresponding gene decreased in response to pharmacological activation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Arkhipov VI, Kapralova MV. Metabotropic glutamate receptors as targets for new drug development. Eksp. Klin. Farmakol. 2011;74(10):46-52. Russian.

    CAS  PubMed  Google Scholar 

  2. Arkhipov VI, Kapralova MV. Expression of metabotropic glutamate receptors after hippocampal injury. Bull. Exp. Biol. Med. 2014;156(4):457-460.

    Article  CAS  PubMed  Google Scholar 

  3. Arkhipov VI, Kapralova MV, Pershina EV. Excitotoxicity and experimental approaches to neuroprotection. Sovremen. Problemy Nauki Obrazovaniya. 2013;(5):486. Russian.

    Google Scholar 

  4. Gordon RYa, Shubina LV, Kapralova MV, Pershina EB, Khutzian SS, Arhipov VI. Peculiarities of neurodegeneration in hippocampus fields after kainic acid action in rats. Tsitologiya. 2014;56(12):919-925. Russian.

    Google Scholar 

  5. Lebedev DS, Arkhipov VI. Expression of mGluR5 and synaptophysin genes after injury to the dorsal Hippocampus, inflicted by cainic acid. Bull. Exp. Biol. Med. 2009;147(2):236-239.

    Article  CAS  PubMed  Google Scholar 

  6. Lebedev DS, Arkhipov VI. Expression of mitochondrial uncoupling protein UCP2 in the brain of rats after hippocampal injury inflicted by kainic acid. Bull. Exp. Biol. Med. 2010;150(2):185-187.

    Article  CAS  PubMed  Google Scholar 

  7. Arkhipov V, Kapralova M, Pershina E, Gordon R. Delayed treatments with pharmacological modulators of pre- and postsynaptic mGlu receptors rescue the hippocampus from kainateinduced neurodegeneration. Neurosci. Lett. 2014;570:5-9.

    Article  CAS  PubMed  Google Scholar 

  8. Gerin CG, Madueke IC, Perkins T, Hill S, Smith K, Haley B, Allen SA, Garcia RP, Paunesku T, Woloschak G. Combination strategies for repair, plasticity, and regeneration using regulation of gene expression during the chronic phase after spinal cord injury. Synapse. 2011;65(12):1255-1281.

    Article  CAS  PubMed  Google Scholar 

  9. Grabenstatter HL, Russek SJ, Brooks-Kayal AR. Molecular pathways controlling inhibitory receptor expression. Epilepsia. 2012;53(Suppl. 9):71-78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mehta A, Prabhakar M, Kumar P, Deshmukh R, Sharma PL. Excitotoxicity: bridge to various triggers in neurodegenerative disorders. Eur. J. Pharm. 2013;698(1-3):6-18.

    Article  CAS  Google Scholar 

  11. Motti D, Le Duigou C, Eugène E, Chemaly N, Wittner L, Lazarevic D, Krmac H, Marstrand T, Valen E, Sanges R, Stupka E, Sandelin A, Cherubini E, Gustincich S, Miles R. Gene expression analysis of the emergence of epileptiform activity after focal injection of kainic acid into mouse hippocampus. Eur. J. Neurosci. 2010;32(8):1364-1379.

    Article  PubMed  Google Scholar 

  12. Niswender CM, Conn PJ. Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu. Rev. Pharmacol. Toxicol. 2010;50:295-322.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Pershina EV, Arkhipov VI. Subacute activation of mGlu4 receptors causes the feedback inhibition of its gene expression in rat brain. Life Sci. 2016;153:50-54.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences; Pushchino State Natural Science Institute, Pushchino, Russia

    E. V. Pershina, M. V. Kapralova & V. I. Arkhipov

Authors
  1. E. V. Pershina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. V. Kapralova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. I. Arkhipov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. I. Arkhipov.

Additional information

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 162, No. 12, pp. 756-759, December, 2016

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pershina, E.V., Kapralova, M.V. & Arkhipov, V.I. Effect of Pharmacological Modulation of Activity of Metabotropic Glutamate Receptors on Their Gene Expression after Excitotoxic Damage in Hippocampal Neurons. Bull Exp Biol Med 162, 784–787 (2017). https://doi.org/10.1007/s10517-017-3713-2

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-017-3713-2

Key Words

Search

Navigation