title: Methamphetamine alters blood brain barrier protein expression in mice, facilitating central nervous system infection by neurotropic Cryptococcus neoformans.
abstract: Methamphetamine (METH) is a drug of abuse that is a potent and highly addictive central nervous system (CNS) stimulant. The blood brain barrier (BBB) is a unique interface that in part functions to prevent microbial invasion of the CNS. The effects of METH on brain vasculature have not been studied extensively. We hypothesized that METH alters the BBB integrity, increasing susceptibility to CNS infection. Using a murine model of METH administration, we demonstrated that METH alters BBB integrity and modifies the expression of tight junction and adhesion molecules. Additionally, we showed that BBB disruption accelerates transmigration of the neurotropic fungus Cryptococcus neoformans into the brain parenchyma after systemic infection. Furthermore, METH-treated mice displayed increased mortality as compared to untreated animals. Our findings provide novel evidence of the impact of METH abuse on the integrity of the cells that comprise the BBB and protect the brain from infection.
authors.affiliation: Public Health Research Institute, Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, Newark, USA.
authors.forename: Eliseo A
authors.initials: EA
authors.lastname: Eugenin
authors.forename: Jade M
authors.initials: JM
authors.lastname: Greco
authors.forename: Susana
authors.initials: S
authors.lastname: Frases
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Nosanchuk
authors.forename: Luis R
authors.initials: LR
authors.lastname: Martinez
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000276:immunology*; D001921:Brain / Q000382:microbiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D000697:Central Nervous System Stimulants / Q000009:adverse effects; D003455:Cryptococcus neoformans / Q000276:immunology*; D005260:Female; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016919:Meningitis, Cryptococcal / Q000276:immunology* / Q000401:mortality; D008694:Methamphetamine / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D014176:Protein Biosynthesis / Q000187:drug effects*; D016019:Survival Analysis; D062725:Tight Junction Proteins / Q000096:biosynthesis
chemical_list: D015815:Cell Adhesion Molecules; D000697:Central Nervous System Stimulants; D007166:Immunosuppressive Agents; D062725:Tight Junction Proteins; D008694:Methamphetamine
keywords: Cryptococcus neoformans; blood brain barrier; methamphetamine