Journal article
Pharmacologically increasing microtubule acetylation corrects stress-exacerbated effects of organophosphates on neurons
Traffic (Copenhagen, Denmark), v 18(7), pp 433-441
Jul 2017
PMID: 28471062
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Many veterans of the 1990-1991 Gulf War contracted Gulf War Illness (GWI), a multisymptom disease that primarily affects the nervous system. Here, we treated cultures of human or rat neurons with diisopropyl fluorophosphate (DFP), an analog of sarin, one of the organophosphate (OP) toxicants to which the military veterans were exposed. All observed cellular defects produced by DFP were exacerbated by pretreatment with corticosterone or cortisol, which, in rat and human neurons, respectively, serves in our experiments to mimic the physical stress endured by soldiers during the war. To best mimic the disease, DFP was used below the level needed to inhibit acetylcholinesterase. We observed a diminution in the ratio of acetylated to total tubulin that was correctable by treatment with tubacin, a drug that inhibits HDAC6, the tubulin deacetylase. The reduction in microtubule acetylation was coupled with deficits in microtubule dynamics, which were correctable by HDAC6 inhibition. Deficits in mitochondrial transport and dopamine release were also improved by tubacin. Thus, various negative effects of the toxicant/stress exposures were at least partially correctable by restoring microtubule acetylation to a more normal status. Such an approach may have therapeutic benefit for individuals suffering from GWI or other neurological disorders linked to OP exposure.
Metrics
Details
- Title
- Pharmacologically increasing microtubule acetylation corrects stress-exacerbated effects of organophosphates on neurons
- Creators
- Anand N Rao - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PennsylvaniaAnkita Patil - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PennsylvaniaZachary D Brodnik - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PennsylvaniaLiang Qiang - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PennsylvaniaRodrigo A España - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PennsylvaniaKimberly A Sullivan - Boston University School of Public Health, Boston, MassachusettsMark M Black - Department of Anatomy and Cell Biology, Temple University, Philadelphia, PennsylvaniaPeter W Baas - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania
- Publication Details
- Traffic (Copenhagen, Denmark), v 18(7), pp 433-441
- Publisher
- Wiley; England
- Grant note
- F31 NS093748 / NINDS NIH HHS R01 NS028785 / NINDS NIH HHS R01 DA031900 / NIDA NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000403215100003
- Scopus ID
- 2-s2.0-85019846065
- Other Identifier
- 991014878063304721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology