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ANXIETY, DEPRESSION, AND MEMORY LOSS IN CHAGAS DISEASE: A PUZZLE FAR BEYOND NEUROINFLAMMATION TO BE UNPICKED AND SOLVED
Problemas neurológicos
Mudanças comportamentais
Distúrbios neurocognitivos
Ansiedade
Depressão
Perda de memória
Modelo pré-clínico
Benznidazol
Imunoterapia
Neurological disorders
Behavioural changes
Neurocognitive disorders
Anxiety
Depression
Memory loss
Preclinical model
Benznidazole
Immunotherapy
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.
Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Laboratório Multidisciplinar de Apoio à Pesquisa em Nefrologia e Ciências Médicas. Niterói, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.
Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Laboratório Multidisciplinar de Apoio à Pesquisa em Nefrologia e Ciências Médicas. Niterói, RJ, Brasil.
Abstract
Mental disorders such as anxiety, depression, and memory loss have been described in patients with chronic Chagas disease
(CD), a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Social, psychological, and biological
stressors may take part in these processes. There is a consensus on the recognition of an acute nervous form of CD. In chronic
CD patients, a neurological form is associated with immunosuppression and neurobehavioural changes as sequelae of stroke.
The chronic nervous form of CD has been refuted, based on the absence of histopathological lesions and neuroinflammation;
however, computed tomography shows brain atrophy. Overall, in preclinical models of chronic T. cruzi infection in the absence
of neuroinflammation, behavioural disorders such as anxiety and depression, and memory loss are related to brain atrophy,
parasite persistence, oxidative stress, and cytokine production in the central nervous system. Interferon-gamma (IFNγ)-bearing
microglial cells are colocalised with astrocytes carrying T. cruzi amastigote forms. In vitro studies suggest that IFNγ fuels
astrocyte infection by T. cruzi and implicate IFNγ-stimulated infected astrocytes as sources of TNF and nitric oxide, which
may also contribute to parasite persistence in the brain tissue and promote behavioural and neurocognitive changes. Preclinical
trials in chronically infected mice targeting the TNF pathway or the parasite opened paths for therapeutic approaches with a
beneficial impact on depression and memory loss. Despite the path taken, replicating aspects of the chronic CD and testing
therapeutic schemes in preclinical models, these findings may get lost in translation as the chronic nervous form of CD does not
fulfil biomedical model requirements, as the presence of neuroinflammation, to be recognised. It is hoped that brain atrophy
and behavioural and neurocognitive changes are sufficient traits to bring the attention of researchers to study the biological and
molecular basis of the central nervous system commitment in chronic CD.
Keywords in Portuguese
Doença de ChagasProblemas neurológicos
Mudanças comportamentais
Distúrbios neurocognitivos
Ansiedade
Depressão
Perda de memória
Modelo pré-clínico
Benznidazol
Imunoterapia
Keywords
Chagas diseaseNeurological disorders
Behavioural changes
Neurocognitive disorders
Anxiety
Depression
Memory loss
Preclinical model
Benznidazole
Immunotherapy
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