Journal article
Transcriptomic profile analysis of brain inferior colliculus following acute hydrogen sulfide exposure
Toxicology (Amsterdam), Vol.430, pp.152345-152345
01/30/2020
DOI: 10.1016/j.tox.2019.152345
PMID: 31843631
Abstract
•Transcriptomic profiling analyses following acute exposure to H2S were performed.•Multiple signaling pathways were dysregulated following H2S exposure.•PI3K/Akt and MAPK signaling pathways were activated after H2S exposure.•MRI scan analysis revealed lesions in the IC and TH following H2S exposure.•Acute H2S exposure induced a neuroinflammatory response.
Hydrogen sulfide (H2S) is a gaseous molecule found naturally in the environment, and as an industrial byproduct, and is known to cause acute death and induces long-term neurological disorders following acute high dose exposures. Currently, there is no drug approved for treatment of acute H2S-induced neurotoxicity and/or neurological sequelae. Lack of a deep understanding of pathogenesis of H2S-induced neurotoxicity has delayed the development of appropriate therapeutic drugs that target H2S-induced neuropathology. RNA sequencing analysis was performed to elucidate the cellular and molecular mechanisms of H2S-induced neurodegeneration, and to identify key molecular elements and pathways that contribute to H2S-induced neurotoxicity. C57BL/6J mice were exposed by whole body inhalation to 700 ppm of H2S for either one day, two consecutive days or 4 consecutive days. Magnetic resonance imaging (MRI) scan analyses showed H2S exposure induced lesions in the inferior colliculus (IC) and thalamus (TH). This mechanistic study focused on the IC. RNA Sequencing analysis revealed that mice exposed once, twice, or 4 times had 283, 193 and 296 differentially expressed genes (DEG), respectively (q-value < 0.05, fold-change> 1.5). Hydrogen sulfide exposure modulated multiple biological pathways including unfolded protein response, neurotransmitters, oxidative stress, hypoxia, calcium signaling, and inflammatory response in the IC. Hydrogen sulfide exposure activated PI3K/Akt and MAPK signaling pathways. Pro-inflammatory cytokines were shown to be potential initiators of the modulated signaling pathways following H2S exposure. Furthermore, microglia were shown to release IL-18 and astrocytes released both IL-1β and IL-18 in response to H2S. This transcriptomic analysis data revealed complex signaling pathways involved in H2S-induced neurotoxicity and may provide important associated mechanistic insights.
Details
- Title: Subtitle
- Transcriptomic profile analysis of brain inferior colliculus following acute hydrogen sulfide exposure
- Creators
- Dong-Suk Kim - Iowa State UniversityPoojya Anantharam - Iowa State UniversityPiyush Padhi - Iowa State UniversityDaniel R Thedens - University of IowaGanwu Li - Iowa State UniversityEbony Gilbreath - Tuskegee UniversityWilson K Rumbeiha - University of California, Davis
- Resource Type
- Journal article
- Publication Details
- Toxicology (Amsterdam), Vol.430, pp.152345-152345
- DOI
- 10.1016/j.tox.2019.152345
- PMID
- 31843631
- NLM abbreviation
- Toxicology
- ISSN
- 0300-483X
- eISSN
- 1879-3185
- Publisher
- Elsevier B.V
- Grant note
- name: the Iowa State University College of Veterinary Medicine Seed; DOI: 10.13039/100011809, name: Tuskegee University
- Language
- English
- Date published
- 01/30/2020
- Academic Unit
- Radiology; Electrical and Computer Engineering
- Record Identifier
- 9984197909702771
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