Premium
Acute Exposure to High Level of Hydrogen Sulfide Induces Neurodegeneration via Activation of Inflammasomes in Brain
Author(s) -
Kim Dongsuk,
Anantharam Poojya V,
Whitley Elizabeth M,
Gilbreath Ebony,
Mahama Belinda Y,
Kanthasamy Arthi,
Rumbeiha Wilson K
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1195.1
Subject(s) - neuroinflammation , downregulation and upregulation , inflammation , neurodegeneration , chemistry , microbiology and biotechnology , biology , immunology , medicine , biochemistry , gene , disease
Hydrogen sulfide (H 2 S) is gaseous molecule and can be produced endogenously playing important roles in cell signaling in mammalians including human. However, acute exposure to high concentrations of H 2 S induces brain damage, including long‐term neurological dysfunction. To better understand the exact cellular and molecular mechanisms of H 2 S‐induced neurological disorders, we investigated neuroinflammation aspect of H 2 S‐induced toxicity using the Qiagen mouse Inflammation Response & Autoimmunity RT 2 Profiler™ PCR array system. C57 black mice were exposed to 310 ppm H 2 S by whole body inhalation for 1, 3 or 7 days for 40 minutes on day 1 and 15 minutes on subsequent days. Hydrogen sulfide‐exposed mice showed significant impairment in motor activity compared to the control. Histopathology revealed neurodegenerative lesions in the central nucleus of the inferior colliculus (IC), and IC was dissected at each terminal endpoint. Quantitative real‐time PCR based array system was performed, and 84 inflammation related genes expressions were analyzed. IL‐18, Myd88, and TLR9 were upregulated, while C3, CCL12, and CXCR4 were downregulated in H 2 S exposed group. Interestingly, all three genes upregulated in H2S‐treated group play important roles in activation of inflammasomes. We further investigated genes relevant to the activation of inflammasomes using quantitative RT‐PCR. IL‐1β, CASP‐1 and AIM2 were upregulated in H 2 S‐treated groups. Expression of NLRP3 was downregulated, whereas NLRC4 was not greatly altered in H 2 S‐treated groups. We also found that NLRP1b, not NLRP1a, was upregulated in H 2 S treated group, while we are characterizing further the activation of inflammasomes and its significance in H 2 S‐induced neurodegeneration. Taken together, our results demonstrated that inhalation exposure to H 2 S induced motor behavioral deficit and neurodegeneration and that inflammasomes may play a significant role in H 2 S‐associated neurological disorders (Iowa State Internal Grant).