Open AccessAlpha-7 nicotinic acetylcholine receptor agonist treatment in a rat model of Huntington's disease and involvement of heme oxygenase-1
Author(s) -
Laura Foucault-Fruchard,
Claire Tronel,
Sylvie Bodard,
Zuhal Gulhan,
Julie Busson,
Sylvie Chalon,
Daniel Antier
Publication year - 2018
Publication title -
neural regeneration research/neural regeneration research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.93
H-Index - 38
eISSN - 1876-7958
pISSN - 1673-5374
DOI - 10.4103/1673-5374.230301
Subject(s) - quinolinic acid , agonist , nicotinic agonist , nicotinic acetylcholine receptor , pharmacology , neuroprotection , striatum , heme oxygenase , cholinergic , neuroinflammation , acetylcholine receptor , medicine , acetylcholine , chemistry , receptor , endocrinology , heme , biochemistry , inflammation , dopamine , tryptophan , enzyme , amino acid
Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases. We recently reported that repeated alpha-7 nicotinic acetylcholine receptor (α7nAChR) activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons. To further investigate the underlying mechanism, we established rat models of early-stage Huntington's disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water, twice a day during 4 days. Western blot assay results showed that the expression of heme oxygenase-1 (HO-1), the key component of the cholinergic anti-inflammatory pathway, in the right striatum of rat models of Huntington's disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water, and that the increase in HO-1 expression was independent of change in α7nAChR expression. These findings suggest that HO-1 expression is unrelated to α7nAChR density and the increase in HO-1 expression likely contributes to α7nAChR activation-related neuroprotective effect in early-stage Huntington's disease.