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PLoS One. 2018 Jan 2;13(1):e0190078. doi: 10.1371/journal.pone.0190078. eCollection 2018.

Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats.

Author information

1
Department of Psychiatry, Rush University Medical Center, Chicago, IL, United States of America.
2
Department of Physician Assistant Studies, Rush University Medical Center, Chicago, IL, United States of America.
3
Center for Compulsive Behavior and Addiction, Rush University Medical Center, Chicago, IL, United States of America.
4
Department of Health Sciences, Rush University Medical Center, Chicago, IL, United States of America.
5
Department of Pharmacology, Rush University Medical Center, Chicago, IL, United States of America.
6
Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, United States of America.

Abstract

The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1), two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults.

PMID:
29293553
PMCID:
PMC5749763
DOI:
10.1371/journal.pone.0190078
[Indexed for MEDLINE]
Free PMC Article

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