Somatostatin and cannabinoid receptors crosstalk in protection of huntingtin knock-in striatal neuronal cells in response to quinolinic acid

Neurochem Int. 2019 Oct:129:104518. doi: 10.1016/j.neuint.2019.104518. Epub 2019 Aug 2.

Abstract

In the present study, we describe the status of somatostatin receptor 2 and 5 (SSTR2 and SSTR5) as well as cannabinoid type 1 receptor (CB1R) in Huntingtin (Htt) knock-in striatal neuronal cells. In mutant Htt (mHtt) knock-in (STHdhQ111/111) and wild type (STHdhQ7/7) striatal neuronal cells, SSTRs and CB1R exhibit prominent cytoplasmic expression and respond to agonist in a receptor specific manner. In response to quinolinic acid (QUIN)-induced toxicity, STHdhQ111/111 cells are more vulnerable and display suppressed cell survival signaling pathways. Receptor-specific agonists protect cells from QUIN-induced toxicity and activate ERK1/2 in both STHdh cells. Co-activation of SSTRs and CB1R resulted in loss of protective effects, delayed ERK1/2 phosphorylation and altered receptor complex composition. These results provide firsthand evidence in support of the protective role of SSTRs in STHdh cells and the possible crosstalk between SSTRs and CB1R in the modulation of excitotoxicity in Huntington's disease.

Keywords: Cannabinoid receptor 1; Excitotoxicity; Huntington's disease; STHdh cells; Somatostatin receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Transformed
  • Corpus Striatum / cytology
  • Corpus Striatum / drug effects*
  • Gene Expression Regulation / drug effects
  • Gene Knock-In Techniques
  • Genes, Reporter
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurotoxins / antagonists & inhibitors
  • Neurotoxins / toxicity*
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Quinolinic Acid / antagonists & inhibitors
  • Quinolinic Acid / toxicity*
  • Receptor Cross-Talk*
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / biosynthesis
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / physiology*
  • Receptors, Somatostatin / agonists
  • Receptors, Somatostatin / biosynthesis
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / physiology*

Substances

  • CNR1 protein, mouse
  • Neurotoxins
  • Receptor, Cannabinoid, CB1
  • Receptors, Somatostatin
  • Sstr2 protein, mouse
  • somatostatin receptor 5
  • Quinolinic Acid