CD38 and MGluR1 as possible signaling molecules involved in epileptogenesis: A potential role for NAD+ homeostasis

Brain Res. 2021 Aug 15:1765:147509. doi: 10.1016/j.brainres.2021.147509. Epub 2021 Apr 28.


In spite of long-term intensive scientific research efforts, there are still many issues concerning the mechanisms of epileptogenesis and epilepsy to be resolved. Temporal lobe, in particular hippocampus, is vulnerable to epileptogenic process. Herein, electrical kindling model of temporal lobe were analyzed using proteomic approach. A dramatic decrease in nicotinamide adenine dinucleotide (NAD+) level was exhibited during the kindling procedure in hippocampus. After stage 3, high CD38 expression was detected by qPCR, nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) and western blot analysis. An increase in expression of CD38/NADase activity was observed during the kindling procedure in hippocampus that suggest it as one of the most important NAD+ degrading enzymes during epileptogenesis. Subsequently, gene expression of CD38 metabolite related proteins (Ryr2, FKBP-12.6, Chrm1, mGluR1 and Cnx43) were examined. Among them, changes in the expression level of mGluR1 was more than other genes, which was also confirmed by LC MS/MS and western blotting analysis. These findings provided valuable information about changes in the expression of CD38/cADPR signaling pathway and suggest its crucial role during epileptogenesis.

Keywords: CD38; Epileptogenesis; Hippocampus; Kindling; LC MS/MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase / metabolism
  • ADP-ribosyl Cyclase 1 / metabolism*
  • Animals
  • Brain / physiology
  • Cyclic ADP-Ribose / analogs & derivatives
  • Cyclic ADP-Ribose / pharmacology
  • Disease Models, Animal
  • Gene Expression / genetics
  • Hippocampus / physiology
  • Homeostasis / physiology
  • Kindling, Neurologic / physiology
  • Male
  • Membrane Glycoproteins / metabolism
  • NAD / metabolism
  • Proteomics / methods
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / metabolism*
  • Seizures / metabolism*
  • Seizures / physiopathology
  • Signal Transduction
  • Tandem Mass Spectrometry / methods


  • Membrane Glycoproteins
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • NAD
  • Cyclic ADP-Ribose
  • ADP-ribosyl Cyclase
  • Cd38 protein, rat
  • ADP-ribosyl Cyclase 1