title: Increased levels of glutamate in the central nervous system are associated with behavioral symptoms in experimental malaria.
abstract: Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection. This condition has been associated with cognitive, behavioral and motor dysfunctions, seizures and coma. The underlying mechanisms of CM are incompletely understood. Glutamate and other metabolites such as lactate have been implicated in its pathogenesis. In the present study, we investigated the involvement of glutamate in the behavioral symptoms of CM. Seventeen female C57BL/6 mice (20-25 g) aged 6-8 weeks were infected with P. berghei ANKA by the intraperitoneal route using a standardized inoculation of 10⁶ parasitized red blood cells suspended in 0.2 mL PBS. Control animals (N = 17) received the same volume of PBS. Behavioral and neurological symptoms were analyzed by the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. Glutamate release was measured in the cerebral cortex and cerebrospinal fluid of infected and control mice by fluorimetric assay. All functional categories of the SHIRPA battery were significantly altered in the infected mice at 6 days post-infection (dpi) (P ≤ 0.05). In parallel to CM symptoms, we found a significant increase in glutamate levels in the cerebral cortex (mean ± SEM; control: 11.62 ± 0.90 nmol/mg protein; infected at 3 dpi: 10.36 ± 1.17 nmol/mg protein; infected at 6 dpi: 26.65 ± 0.73 nmol/mg protein; with EGTA, control: 5.60 ± 1.92 nmol/mg protein; infected at 3 dpi: 6.24 ± 1.87 nmol/mg protein; infected at 6 dpi: 14.14 ± 0.84 nmol/mg protein) and in the cerebrospinal fluid (control: 128 ± 51.23 pmol/mg protein; infected: 301.4 ± 22.52 pmol/mg protein) of infected mice (P ≤ 0.05). These findings suggest a role of glutamate in the central nervous system dysfunction found in CM.
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil. alines.miranda@hotmail.com
authors.forename: A S
authors.initials: AS
authors.lastname: Miranda
authors.forename: L B
authors.initials: LB
authors.lastname: Vieira
authors.forename: N
authors.initials: N
authors.lastname: Lacerda-Queiroz
authors.forename: A H
authors.initials: AH
authors.lastname: Souza
authors.forename: D H
authors.initials: DH
authors.lastname: Rodrigues
authors.forename: M C
authors.initials: MC
authors.lastname: Vilela
authors.forename: M V
authors.initials: MV
authors.lastname: Gomez
authors.forename: F S
authors.initials: FS
authors.lastname: Machado
authors.forename: M A
authors.initials: MA
authors.lastname: Rachid
authors.forename: A L
authors.initials: AL
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D001526:Behavioral Symptoms / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000737:chemistry*; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D016779:Malaria, Cerebral / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei
chemical_list: D018698:Glutamic Acid