Medial Septal NMDA Glutamate Receptors are Involved in Modulation of Blood Natural Killer Cell Activity in Rats

J Neuroimmune Pharmacol. 2016 Mar;11(1):121-32. doi: 10.1007/s11481-015-9632-y. Epub 2015 Oct 10.

Abstract

The purpose of the present study was to determine the specific role of the medial septal (MS) NMDA glutamate receptors on peripheral blood natural killer cell cytotoxicity (NKCC) and their (large granular lymphocyte, LGL) number, as well as the plasma concentration of tumor necrosis factor α (TNF-α) and corticosterone in male Wistar rats exposed to elevated plus maze (EPM) stress or non-stress conditions. The NMDA groups were injected with NMDA glutamate receptor agonist (N-methyl-D-aspartate; 0.25 μg/rat), the D-AP7 group was injected with DL-2-amino-7-phosphoheptanoate (0.1 μg/rat), an antagonist of NMDA glutamate receptors, and the control Sal group with saline (0.5 μl/rat) via previously implanted cannulae into the MS. There was an increase in the NKCC, NK/LGL number and plasma TNF-α concentration after the NMDA injections, being much stronger within the rats under non-stress conditions rather than the rats exposed to EPM stress. These parameters were decreased in the D-AP7 rats, suggesting receptor/ion channel specificity. Moreover, a lower plasma corticosterone concentration within the NMDA rather than the Sal and D-AP7 groups was found. The obtained results suggest that activation of the NMDA glutamate receptors in the MS, accompanied by changes in the corticosterone and cytokine responses, may be involved in modulation of the blood natural anti-tumor response, under EPM stress and non-stress conditions.

Keywords: Medial septum, elevated plus maze, anxiety, NK cells, tumor necrosis factor-α; NMDA receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corticosterone / blood
  • Cytotoxicity, Immunologic / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Excitatory Amino Acid Agonists / administration & dosage
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Injections, Intraventricular
  • Killer Cells, Natural / immunology*
  • Male
  • Maze Learning / drug effects
  • Neuroimmunomodulation / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / immunology*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Septal Nuclei / immunology*
  • Septal Nuclei / metabolism
  • Stress, Psychological / immunology*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Tumor Necrosis Factor-alpha
  • Corticosterone