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NEUROLOGICAL IMPAIRMENT CAUSED BY SCHISTOSOMA MANSONI SYSTEMIC INFECTION EXHIBITS EARLY FEATURES OF IDIOPATHIC NEURODEGENERATIVE DISEASE
Comprometimento neurológico
Infecção sistêmica
Idiopática doença neurodegenerativa
Neurological impairment
Idiopathic neurodegenerative disease
Systemic infection
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Abstract
Schistosomiasis, a neglected tropical disease caused by trem atodes of the Schistosoma genus, affects over 250 million people
around the world. This disease has been associated with learning
and memory deficits in children, whereas reduced attention
levels, impaired work capacity, and cognitive deficits have been
observed in adults. Strongly correlated with poverty and lack of
basic sanitary conditions, this chronic endemic infection is
common in Africa, South America, and parts of Asia and con tributes to inhibition of social development and low quality of
life in affected areas. Nonetheless, studies on the mechanisms
involved in the neurological impairment caused by schistoso miasis are scarce. Here, we used a murine model of infection
with Schistosoma mansoni in which parasites do not invade the
central nervous system to evaluate the consequences of systemic
infection on neurologic function. We observed that systemic
infection with S. mansoni led to astrocyte and microglia activa tion, expression of oxidative stress-induced transcription factor
Nrf2, oxidative damage, Tau phosphorylation, and amyloid-β
peptide accumulation in the prefrontal cortex of infected ani mals. We also found impairment in spatial learning and memory
as evaluated by the Morris water maze task. Administration of
anthelmintic (praziquantel) and antioxidant (N-acetylcysteine
plus deferoxamine) treatments was effective in inhibiting most
of these phenotypes, and the combination of both treatments
had a synergistic effect to prevent such changes. These data
demonstrate new perspectives toward the understanding of the
pathology and possible therapeutic approaches to counteract
long-term effects of systemic schistosomiasis on brain function.
Keywords in Portuguese
Schistosoma mansoniComprometimento neurológico
Infecção sistêmica
Idiopática doença neurodegenerativa
Keywords
Schistosoma mansoniNeurological impairment
Idiopathic neurodegenerative disease
Systemic infection
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