RESUMO
Toxoplasma gondii is able to manipulate the host immune system to establish a persistent and efficient infection, contributing to the development of brain abnormalities with behavioral repercussions. In this context, this work aimed to evaluate the effects of T. gondii infection on the systemic inflammatory response and structure of the primary somatosensory cortex (PSC). C57BL/6 and BALB/c mice were infected with T. gondii ME49 strain tissue cysts and accompanied for 30 days. After this period, levels of cytokines IFN-γ, IL-12, TNF-α and TGF-ß were measured. After blood collection, mice were perfused and the brains were submitted to immunohistochemistry for perineuronal net (PNN) evaluation and cyst quantification. The results showed that C57BL/6 mice presented higher levels of TNF-α and IL-12, while the levels of TGF-ß were similar between the two mouse lineages, associated with the elevated number of tissue cysts, with a higher occurrence of cysts in the posterior area of the PSC when compared to BALB/c mice, which presented a more homogeneous cyst distribution. Immunohistochemistry analysis revealed a greater loss of PNN labeling in C57BL/6 animals compared to BALB/c. These data raised a discussion about the ability of T. gondii to stimulate a systemic inflammatory response capable of indirectly interfering in the brain structure and function.
Assuntos
Córtex Somatossensorial , Síndrome de Resposta Inflamatória Sistêmica , Toxoplasma , Toxoplasmose , Animais , Camundongos , Interleucina-12/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Córtex Somatossensorial/imunologia , Córtex Somatossensorial/parasitologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/parasitologia , Toxoplasma/patogenicidade , Toxoplasmose/imunologia , Toxoplasmose/parasitologia , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Behavioral and neurochemical alterations associated with toxoplasmosis may be influenced by the persistence of tissue cysts and activation of an immune response in the brain of Toxoplasma gondii-infected hosts. The cerebral extracellular matrix is organised as perineuronal nets (PNNs) that are both released and ensheath by some neurons and glial cells. There is evidences to suggest that PNNs impairment is a pathophysiological mechanism associated with neuropsychiatric conditions. However, there is a lack of information regarding the impact of parasitic infections on the PNNs integrity and how this could affect the host's behavior. OBJECTIVES: In this context, we aimed to analyse the impact of T. gondii infection on cyst burden, PNNs integrity, and possible effects in the locomotor activity of chronically infected mice. METHODS: We infected mice with T. gondii ME-49 strain. After thirty days, we assessed locomotor performance of animals using the open field test, followed by evaluation of cysts burden and PNNs integrity in four brain regions (primary and secondary motor cortices, prefrontal and somesthetic cortex) to assess the PNNs integrity using Wisteria floribunda agglutinin (WFA) labeling by immunohistochemical analyses. FINDINGS AND MAIN CONCLUSIONS: Our findings revealed a random distribution of cysts in the brain, the disruption of PNNs surrounding neurons in four areas of the cerebral cortex and hyperlocomotor behavior in T. gondii-infected mice. These results can contribute to elucidate the link toxoplasmosis with the establishment of neuroinflammatory response in neuropsychiatric disorders and to raise a discussion about the mechanisms related to changes in brain connectivity, with possible behavioral repercussions during chronic T. gondii infection.
Assuntos
Cerebelo/metabolismo , Matriz Extracelular/metabolismo , Neurônios Motores/citologia , Neurônios/patologia , Toxoplasmose Animal , Toxoplasmose/patologia , Animais , Cerebelo/citologia , Modelos Animais de Doenças , Camundongos , Neurônios Motores/metabolismo , Neurônios/metabolismo , Toxoplasma , Toxoplasmose/metabolismoRESUMO
BACKGROUND Behavioral and neurochemical alterations associated with toxoplasmosis may be influenced by the persistence of tissue cysts and activation of an immune response in the brain of Toxoplasma gondii-infected hosts. The cerebral extracellular matrix is organised as perineuronal nets (PNNs) that are both released and ensheath by some neurons and glial cells. There is evidences to suggest that PNNs impairment is a pathophysiological mechanism associated with neuropsychiatric conditions. However, there is a lack of information regarding the impact of parasitic infections on the PNNs integrity and how this could affect the host's behavior. OBJECTIVES In this context, we aimed to analyse the impact of T. gondii infection on cyst burden, PNNs integrity, and possible effects in the locomotor activity of chronically infected mice. METHODS We infected mice with T. gondii ME-49 strain. After thirty days, we assessed locomotor performance of animals using the open field test, followed by evaluation of cysts burden and PNNs integrity in four brain regions (primary and secondary motor cortices, prefrontal and somesthetic cortex) to assess the PNNs integrity using Wisteria floribunda agglutinin (WFA) labeling by immunohistochemical analyses. FINDINGS AND MAIN CONCLUSIONS Our findings revealed a random distribution of cysts in the brain, the disruption of PNNs surrounding neurons in four areas of the cerebral cortex and hyperlocomotor behavior in T. gondii-infected mice. These results can contribute to elucidate the link toxoplasmosis with the establishment of neuroinflammatory response in neuropsychiatric disorders and to raise a discussion about the mechanisms related to changes in brain connectivity, with possible behavioral repercussions during chronic T. gondii infection.
Assuntos
Animais , Camundongos , Cerebelo/metabolismo , Toxoplasmose/patologia , Toxoplasmose Animal , Matriz Extracelular/metabolismo , Neurônios Motores/citologia , Neurônios/patologia , Toxoplasma , Cerebelo/citologia , Toxoplasmose/metabolismo , Modelos Animais de Doenças , Neurônios Motores/metabolismo , Neurônios/metabolismoRESUMO
Episodic-like memory refers to integration of where and when a certain event (what) happened. The glutamatergic neurotransmission, particularly AMPA and NMDA receptors, in the dorsal hippocampus mediates episodic recall. Ketamine is a non-competitive NMDA antagonist with effect on cognitive performance and plasticity. The goal of this study was to evaluate the acute action of ketamine on behavioural and neurochemical aspects of episodic-like memory (WWWhen/ELM task) through immediate-early gene expression (IEG), c-Fos, in the dorsal hippocampus. Animals received saline 0.9% or ketamine at 8 mg/kg or 15 mg/kg (i.p.) immediately after the second sample. Our data indicate that untreated and saline rats integrate the three elements of episodic-like memory. Conversely, animals treated with ketamine showed impairment of ELM formation. In addition, the highest dose of ketamine increased c-Fos expression in dorsal CA1 subregion when compared to saline rats. Our results indicate that the antagonism of NMDA concurrently impair ELM formation of all three aspects of ELM and increase neuronal activation in dorsal CA1.
Assuntos
Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Ketamina/efeitos adversos , Transtornos da Memória/induzido quimicamente , Memória Episódica , Psicotrópicos/efeitos adversos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Anestésicos Dissociativos/efeitos adversos , Animais , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/patologia , Relação Dose-Resposta a Droga , Masculino , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
Many environmental factors contribute to an effective immune response against Toxoplasma gondii (Tg) infection, among which diet is important in triggering the immune response of the host to infection. Emerging reports suggest that salt intake undermines the regulatory mechanisms mediated by innate and adaptive immune cells. Unfortunately, the impact of an Intermediate Salt Diet (ISD) on the pathogenesis and immune response to toxoplasmosis remains unclear. The purpose of this study was to evaluate the susceptibility profile to an ISD (NaCl 2%) of two mouse strains (outbred Swiss and inbred C57BL6) infected by the ME49 strain of Tg. Our data confirm an antagonistic susceptibility to oral Tg infection among the two mouse strains. Sodium intake induced the highest mortality in C57BL6 compared to Swiss mice in the infected groups. A simultaneous ISD with the infection did not induce significant differences in body weight in either mouse strains. Both mouse strains showed an antagonistic response to a sodium intake diet on the number of parasite brain cysts. An increased number of brain cysts in C57BL6 ISD-Tg animals were noted while Swiss ISD-Tg animals presented a decrease in the number of brain cysts compared to NSD-Tg (Normal Salt Diet) for both mouse strains. Furthermore, sodium intake caused a significant reduction in the specific humoral immune response against Tg in inbred C57BL6 mice. Thus, our data reveal that an ISD affects the humoral immune response in the murine model and influences the course of Tg infection.