Increased levels of glutamate in the central nervous system are associated with behavioral symptoms in experimental malaria
AUTOR(ES)
Miranda, A.S., Vieira, L.B., Lacerda-Queiroz, N., Souza, A.H., Rodrigues, D.H., Vilela, M.C., Gomez, M.V., Machado, F.S., Rachid, M.A., Teixeira, A.L.
FONTE
Brazilian Journal of Medical and Biological Research
DATA DE PUBLICAÇÃO
2010-12
RESUMO
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 10(6) 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.
Documentos Relacionados
- Reovirus infection and tissue injury in the mouse central nervous system are associated with apoptosis.
- Demyelinating lesions due to Theiler's virus are associated with ongoing central nervous system infection.
- Strychnine Binding Associated with Glycine Receptors of the Central Nervous System
- Sarcoidosis of the breast, central nervous system, and exocrine glands in a patient with sicca symptoms.
- Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system.