Improvement of Impaired Electrical Activity in NPC1 Mutant Cortical Neurons Upon DHPG Stimulation Detected by Micro-Electrode Array

Brain Res. 2018 Sep 1;1694:87-93. doi: 10.1016/j.brainres.2018.05.009. Epub 2018 May 16.


Niemann-Pick Type C1 (NPC1) disease is an autosomal recessive neurodegenerative disease characterized by an excessive accumulation of unesterified cholesterol in late endosomes/lysosomes. Patients with NPC1 disease show a series of symptoms in neuropathology, including a gradually increased loss of motor control and seizures. However, mechanism of the neurological manifestations in NPC1 disease is not fully understood yet. In this study, we utilized the micro-electrode array (MEA) to analyze the spontaneous extracellular electrical activity in cultivated cortical neurons of the NPC1 mutant (NPC1-/-) mouse. Our results show a decrease of the spontaneous electrical activity in NPC1-/- neuronal network when compared to wild type neurons, as indicated by the decreased spike rate, burst rate, event rate, and the increased burst period and event period. Application of 3,5-dihydroxyphenylglycine (DHPG), a specific agonist of group I metabotropic glutamate receptors, improved the electrical activity of the NPC1-/- neuronal network, suggesting that DHPG can be used as a potential therapeutic strategy for recovery of the electrical activity in NPC1 disease.

Keywords: Cortical neuron; DHPG; Electrical activity; Group I mGluRs; MEA; NPC1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / drug effects
  • Carrier Proteins / genetics
  • Endosomes / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Membrane Glycoproteins / metabolism
  • Methoxyhydroxyphenylglycol / analogs & derivatives*
  • Methoxyhydroxyphenylglycol / pharmacology
  • Mice, Transgenic
  • Neurons / drug effects*
  • Neurons / physiology
  • Niemann-Pick Disease, Type C / drug therapy
  • Proteins / drug effects*
  • Proteins / genetics*
  • Proteins / metabolism


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Npc1 protein, mouse
  • Proteins
  • Methoxyhydroxyphenylglycol
  • 3,4-dihydroxyphenylglycol