Mast cells and histamine are involved in the neuronal damage observed in a quinolinic acid-induced model of Huntington's disease

J Neurochem. 2022 Jan;160(2):256-270. doi: 10.1111/jnc.15527. Epub 2021 Oct 31.

Abstract

Huntington´s disease (HD) is a pathological condition that can be studied in mice by the administration of quinolinic acid (QUIN), an agonist of the N-methyl-d-aspartate receptor (NMDAR) that induces NMDAR-mediated cytotoxicity and neuroinflammation. Mast cells (MCs) participate in numerous inflammatory processes through the release of important amounts of histamine (HA). In this study, we aimed to characterize the participation of MCs and HA in the establishment of neural and oxidative damage in the QUIN-induced model of HD. C57BL6/J mice (WT), MC-deficient c-KitW-sh/W-sh (Wsh) mice and Wsh mice reconstituted by intracerebroventricular (i.c.v.) injection of 5 × 105 bone marrow-derived mast cells (BMMCs), or i.c.v. administered with HA (5 µg) were used. All groups of animals were intrastriatally injected with 1 µL QUIN (30 nmol/µL) and 3 days later, apomorphine-induced circling behavior, striatal GABA levels and the number of Fluoro-Jade positive cells, as indicators of neuronal damage, were determined. Also, lipid peroxidation (LP) and reactive oxygen species production (ROS), as markers of oxidative damage, were analyzed. Wsh mice showed less QUIN-induced neuronal and oxidative damage than WT and Wsh-MC reconstituted animals. Histamine administration restored the QUIN-induced neuronal and oxidative damage in the non-reconstituted Wsh mice to levels equivalent or superior to those observed in WT mice. Our results demonstrate that MCs and HA participate in the neuronal and oxidative damages observed in mice subjected to the QUIN -induced model of Huntington's disease.

Keywords: Huntington disease; histamine; mast cell; oxidative damage; quinolinic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Histamine / immunology*
  • Histamine / metabolism
  • Huntington Disease / chemically induced
  • Huntington Disease / immunology*
  • Huntington Disease / pathology*
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neurons / pathology*
  • Quinolinic Acid / toxicity

Substances

  • Histamine
  • Quinolinic Acid