RESUMO
Sphingosine-1-phosphate (S1P) is a signaling lipid mediator that is involved in multiple biological processes. The S1P/S1P receptor (S1PR) signaling pathway has an important role in the central nervous system. It contributes to physiologic cellular homeostasis and is also associated with neuroinflammation. Therefore, this study was performed to evaluate the expression of S1PR in dogs with meningoencephalitis of unknown etiology (MUE) and experimental autoimmune encephalomyelitis (EAE). The analysis used 12 brain samples from three neurologically normal dogs, seven dogs with MUE, and two canine EAE models. Anti-S1PR1 antibody was used for immunohistochemistry. In normal brain tissues, S1PR1s were expressed on neurons, astrocytes, oligodendrocytes, and endothelial cells. In MUE and EAE lesions, there was positive staining of S1PR1 on leukocytes. Furthermore, the expression of S1PR1 on neurons, astrocytes, oligodendrocytes, and endothelial cells was upregulated compared to normal brains. This study shows that S1PR1s are expressed in normal brain tissues and leukocytes in inflammatory lesions, and demonstrates the upregulation of S1PR1 expression on nervous system cells in inflammatory lesions of MUE and EAE. These findings indicate that S1P/S1PR signaling pathway might involve physiologic homeostasis and neuroinflammation and represent potential targets for S1PR modulators to treat MUE.
Assuntos
Encéfalo , Doenças do Cão , Encefalomielite Autoimune Experimental , Receptores de Esfingosina-1-Fosfato , Animais , Cães , Doenças do Cão/metabolismo , Encefalomielite Autoimune Experimental/veterinária , Encefalomielite Autoimune Experimental/metabolismo , Encéfalo/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , Feminino , Masculino , Meningoencefalite/veterinária , Meningoencefalite/metabolismo , Doenças Neuroinflamatórias/veterinária , Doenças Neuroinflamatórias/metabolismo , Astrócitos/metabolismoRESUMO
The lack of therapeutics that prevent the development of epilepsy, improve disease prognosis or overcome drug resistance represents an unmet clinical need in veterinary as well as in human medicine. Over the past decade, experimental studies and studies in human epilepsy patients have demonstrated that neuroinflammatory processes are involved in epilepsy development and play a key role in neuronal hyperexcitability that underlies seizure generation. Targeting neuroinflammatory signaling pathways may provide a basis for clinically relevant disease-modification strategies in general, and moreover, could open up new therapeutic avenues for human and veterinary patients with drug-resistant epilepsy. A sound understanding of the neuroinflammatory mechanisms underlying seizure pathogenesis in canine patients is therefore essential for mechanism-based discovery of selective epilepsy therapies that may enable the development of new disease-modifying treatments. In particular, subgroups of canine patients in urgent needs, e.g. dogs with drug-resistant epilepsy, might benefit from more intensive research in this area. Moreover, canine epilepsy shares remarkable similarities in etiology, disease manifestation, and disease progression with human epilepsy. Thus, canine epilepsy is discussed as a translational model for the human disease and epileptic dogs could provide a complementary species for the evaluation of antiepileptic and antiseizure drugs. This review reports key preclinical and clinical findings from experimental research and human medicine supporting the role of neuroinflammation in the pathogenesis of epilepsy. Moreover, the article provides an overview of the current state of knowledge regarding neuroinflammatory processes in canine epilepsy emphasizing the urgent need for further research in this specific field. It also highlights possible functional impact, translational potential and future perspectives of targeting specific inflammatory pathways as disease-modifying and multi-target treatment options for canine epilepsy.
Assuntos
Doenças do Cão , Epilepsia Resistente a Medicamentos , Epilepsia , Cães , Humanos , Animais , Doenças Neuroinflamatórias/veterinária , Epilepsia/veterinária , Epilepsia/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Convulsões/veterinária , Epilepsia Resistente a Medicamentos/veterinária , Doenças do Cão/tratamento farmacológico , Doenças do Cão/etiologiaRESUMO
Whey protein powder (PP), which is mainly derived from bovine milk, is rich in milk fat globule membrane (MFGM). The MGFM has been shown to play a role in promoting neuronal development and cognition in the infant brain. However, its role in Alzheimer's disease (AD) has not been elucidated. Here, we showed that the cognitive ability of 3×Tg-AD mice (a triple-transgenic mouse model of AD) could be improved by feeding PP to mice for 3 mo. In addition, PP ameliorated amyloid peptide deposition and tau hyperphosphorylation in the brains of AD mice. We found that PP could alleviate AD pathology by inhibiting neuroinflammation through the peroxisome proliferator-activated receptor γ (PPARγ)-nuclear factor-κB signaling pathway in the brains of AD mice. Our study revealed an unexpected role of PP in regulating the neuroinflammatory pathology of AD in a mouse model.
Assuntos
Doença de Alzheimer , Humanos , Camundongos , Animais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Doença de Alzheimer/veterinária , PPAR gama , Proteínas do Soro do Leite , Pós , Doenças Neuroinflamatórias/veterinária , Proteínas tau/metabolismo , Camundongos Transgênicos , Transdução de Sinais , Modelos Animais de DoençasRESUMO
High ambient temperature (heat stress, HS) is one of the critical environmental factors causing gut microbiota dysbiosis and increasing gut permeability, consequently inciting neuroinflammation in humans and various animals including chickens. The aim of this study was to examine if a probiotic, Bacillus subtilis, can reduce neuroinflammation in heat-stressed broiler chickens. Two hundred and forty 1-d-old broiler chicks were randomly assigned to 48 pens among 4 treatments in 2 identical, thermal-controlled rooms (n = 12): Thermoneutral (TN)-regular diet (RD), TN-PD (the regular diet mixed with a probiotic at 250 ppm), HS-RD, and HS-PD. The probiotic diet was fed from d 1, and HS at 32°C for 10-h daily was applied from d 15 for a 43-day trial. Results showed that compared to the TN broilers, the HS broilers had higher hippocampal interleukin (IL)-6, toll-like receptor (TLR)4, and heat shock protein (HSP)70 at both mRNA and protein levels regardless of dietary treatment (P < 0.05). In addition, the HS-PD broilers had higher levels of hippocampal IL-8 (P < 0.05) than the TN-PD broilers. Within the HS groups, compared to the HS-RD broilers, the HS-PD broilers had lower levels of IL-6, IL-8, HSP70, and TLR4 (P < 0.05) in the hippocampus. Within the TN groups, the TN-PD broilers had lower IL-8 at both mRNA expressions and protein levels (P < 0.05) but higher TLR4 protein levels (P < 0.05) in the hippocampus as compared to the TN-RD broilers. These results indicate that dietary supplementation of the Bacillus subtilis-based probiotic may reduce HS-induced brain inflammatory reactions in broilers via the gut-brain-immune axis. These results indicate the potential use of probiotics as a management strategy for reducing the impact of HS on poultry production.
Assuntos
Microbioma Gastrointestinal , Probióticos , Animais , Ração Animal/análise , Bacillus subtilis/metabolismo , Encéfalo/metabolismo , Galinhas/genética , Dieta/veterinária , Suplementos Nutricionais , Resposta ao Choque Térmico , Hipocampo , Temperatura Alta , Proteínas de Choque Térmico HSP70/genética , Interleucina-8/metabolismo , Doenças Neuroinflamatórias/veterinária , Probióticos/farmacologia , RNA Mensageiro/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
Autoimmune encephalitis refers to a group of disorders characterised by a non-infectious encephalitis, often with prominent seizures and surface neuronal autoantibodies. AE is an important cause of new-onset refractory status epilepticus in humans and is frequently responsive to immunotherapies including corticosteroids, plasma exchange, intravenous immunoglobulin G and rituximab. Recent research suggests that parallel autoantibodies can be detected in non-human mammalian species. The best documented example is leucine-rich glioma-inactivated 1 (LGI1)-antibodies in domestic cats with limbic encephalitis (LE). In this review, we discuss the role of neuroinflammation and autoantibodies in human and feline epilepsy and LE.
Assuntos
Doenças do Gato , Encefalite , Epilepsia , Encefalite Límbica , Humanos , Gatos , Animais , Doenças Neuroinflamatórias/veterinária , Encefalite Límbica/veterinária , Encefalite/terapia , Encefalite/veterinária , Autoanticorpos , Epilepsia/terapia , Epilepsia/veterinária , Mamíferos , Doenças do Gato/etiologia , Doenças do Gato/terapiaRESUMO
Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a recently emerging bat-borne coronavirus responsible for high mortality rates in piglets. In vitro studies have indicated that SADS-CoV has a wide tissue tropism in different hosts, including humans. However, whether this virus potentially threatens other animals remains unclear. Here, we report the experimental infection of wild-type BALB/c and C57BL/6J suckling mice with SADS-CoV. We found that mice less than 7 days old are susceptible to the virus, which caused notable multitissue infections and damage. The mortality rate was the highest in 2-day-old mice and decreased in older mice. Moreover, a preliminary neuroinflammatory response was observed in 7-day-old SADS-CoV-infected mice. Thus, our results indicate that SADS-CoV has potential pathogenicity in young hosts. IMPORTANCE SADS-CoV, which likely has originated from bat coronaviruses, is highly pathogenic to piglets and poses a threat to the swine industry. Little is known about its potential to disseminate to other animals. No efficient treatment is available, and the quarantine strategy is the only preventive measure. In this study, we demonstrated that SADS-CoV can efficiently replicate in suckling mice younger than 7 days. In contrast to infected piglets, in which intestinal tropism is shown, SADS-CoV caused infection and damage in all murine tissues evaluated in this study. In addition, neuroinflammatory responses were detected in some of the infected mice. Our work provides a preliminary cost-effective model for the screening of antiviral drugs against SADS-CoV infection.
Assuntos
Alphacoronavirus , Infecções por Coronavirus , Diarreia , Camundongos , Doenças dos Suínos , Alphacoronavirus/patogenicidade , Animais , Quirópteros/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Diarreia/complicações , Diarreia/veterinária , Diarreia/virologia , Humanos , Camundongos/virologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias/complicações , Doenças Neuroinflamatórias/veterinária , Doenças Neuroinflamatórias/virologia , Suínos/virologia , Doenças dos Suínos/virologiaRESUMO
Maternal sleep deprivation (MSD) is a global public health problem that affects the physical and mental development of pregnant women and their newborns. The latest research suggests that sleep deprivation (SD) disrupts the gut microbiota, leading to neuroinflammation and psychological disturbances. However, it is unclear whether MSD affects the establishment of gut microbiota and neuroinflammation in the newborns. In the present study, MSD was performed on pregnant Sprague-Dawley rats in the third trimester of pregnancy (gestational days 15-21), after which intestinal contents and brain tissues were collected from offspring at different postnatal days (P1, P7, P14, and P56). Based on microbial profiling, microbial diversity and richness increased in pregnant rats subjected to MSD, as reflected by the significant increase in the phylum Firmicutes. In addition, microbial dysbiosis marked by abundant Firmicutes bacteria was observed in the MSD offspring. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) showed that the expression levels of proinflammatory cytokines interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α) were significantly higher in the MSD offspring at adulthood (P56) than in the control group. Through Spearman correlation analysis, IL-1ß and TNF-α were also shown to be positively correlated with Ruminococcus_1 and Ruminococcaceae_UCG-005 at P56, which may determine the microbiota-host interactions in MSD-related neuroinflammation. Collectively, these results indicate that MSD changes maternal gut microbiota and affects the establishment of neonatal gut microbiota, leading to neuroinflammation in MSD offspring. Therefore, understanding the role of gut microbiota during physiological development may provide potential interventions for cognitive dysfunction in MSD-impacted offspring.
Assuntos
Microbioma Gastrointestinal , Doenças dos Roedores , Animais , Disbiose/etiologia , Disbiose/veterinária , Feminino , Microbioma Gastrointestinal/fisiologia , Humanos , Doenças Neuroinflamatórias/veterinária , Gravidez , Ratos , Ratos Sprague-Dawley , Privação do Sono/complicações , Privação do Sono/veterináriaRESUMO
In this study we describe 207 cases of neuroinflammatory diseases of the central nervous system (CNS) in dogs autopsied at the Athens Veterinary Diagnostic Laboratory (University of Georgia, United States) from 2008 to 2019. Idiopathic and infectious diseases were diagnosed in 111 cases (53.6%) and 96 cases (46.4%), respectively. Idiopathic diseases consisted of granulomatous meningoencephalomyelitis (n = 42; 37.8% of idiopathic cases), nonspecific lymphoplasmacytic meningoencephalomyelitis (n = 39; 35.1%), necrotizing meningoencephalomyelitis (n = 22; 19.8%), presumed steroid-responsive meningitis-arteritis (n = 6; 5.4%), and necrotizing leukoencephalitis (n = 2; 1.8%). Infectious diseases consisted of bacterial infections (n = 49; 51% of infectious cases), viral infections (n = 39; 40.6%), fungal infections (n = 5; 5.2%), and parasitic infections (n = 3; 3.1%). Our study provides an overview of the most frequent neuroinflammatory diseases of the CNS of dogs in our diagnostic routine; indicates that a comprehensive diagnostic approach, including a thorough evaluation of the pathology findings and ancillary laboratory testing results, is important for an adequate diagnosis of neurologic diseases in dogs; and underscores the problems associated with the variability in tissue sample collection methods among cases. The great number of nonspecific lymphoplasmacytic meningoencephalitis also highlights the need for development of molecular laboratory tests to identify potential infectious agents in these cases.
Maladies neuro-inflammatoires du système nerveux central du chien : étude rétrospective de 207 cas (20082019). Dans cette étude, nous décrivons 207 cas de maladies neuro-inflammatoires du système nerveux central (SNC) chez des chiens autopsiés au Athens Veterinary Diagnostic Laboratory (University of Georgia, États-Unis) de 2008 à 2019. Des maladies idiopathiques et infectieuses ont été diagnostiquées dans 111 cas (53,6 %) et 96 cas (46,4 %), respectivement. Les maladies idiopathiques consistaient en : méningo-encéphalomyélite granulomateuse (n = 42; 37,8 % des cas idiopathiques), méningo-encéphalomyélite lymphoplasmocytaire non spécifique (n = 39; 35,1 %), méningo-encéphalomyélite nécrosante (n = 22; 19,8 %), méningite-artérite corticosensible présumée (n = 6; 5,4 %) et leucoencéphalite nécrosante (n = 2; 1,8 %). Les maladies infectieuses comprenaient des infections bactériennes (n = 49; 51 % des cas infectieux), des infections virales (n = 39; 40,6 %), des infections fongiques (n = 5; 5,2 %), et des infections parasitaires (n = 3; 3,1 %). Notre étude donne un aperçu des maladies neuro-inflammatoires du SNC des chiens les plus fréquentes dans notre routine de diagnostic; indique qu'une approche diagnostique complète, comprenant une évaluation approfondie des résultats de la pathologie et des résultats des tests de laboratoire auxiliaires, est importante pour un diagnostic adéquat des maladies neurologiques chez les chiens; et souligne les problèmes associés à la variabilité des méthodes de prélèvement d'échantillons de tissus entre les cas. Le grand nombre de méningo-encéphalites lymphoplasmocytaires non spécifiques souligne également la nécessité de développer des tests de laboratoire moléculaire pour identifier les agents infectieux potentiels dans ces cas.(Traduit par Dr Serge Messier).
Assuntos
Doenças do Sistema Nervoso Central , Doenças do Cão , Meningoencefalite , Animais , Sistema Nervoso Central/patologia , Doenças do Sistema Nervoso Central/epidemiologia , Doenças do Sistema Nervoso Central/veterinária , Doenças do Cão/diagnóstico , Doenças do Cão/epidemiologia , Doenças do Cão/patologia , Cães , Meningoencefalite/diagnóstico , Meningoencefalite/epidemiologia , Meningoencefalite/veterinária , Doenças Neuroinflamatórias/veterinária , Estudos RetrospectivosRESUMO
Purpose: Traumatic brain injury (TBI) is a major cause of death and disability. Cerebrolysin (CBL) has been reported to be anti-inflammatory by reducing reactive oxygen species (ROS) production. However, the neuroprotection of CBL in TBI and the potential mechanism are unclear. We aimed to investigate the neuroprotection and mechanisms of CBL in TBI. Methods: The TBI model was established in strict accordance with the Feeney weight-drop model of focal injury. The neurological score, brain water content, neuroinflammatory cytokine levels, and neuronal damage were evaluated. The involvement of the early brain injury modulatory pathway was also investigated. Results: Following TBI, the results showed that CBL administration increased neurological scores and decreased brain edema by alleviating bloodbrain barrier (BBB) permeability, upregulating tight junction protein (ZO1) levels, and decreasing the levels of the inflammatory cytokines tumor necrosis factorα (TNFα), interleukin1ß (IL1ß), IL6, and NFκB. The TUNEL assay showed that CBL decreased hippocampal neuronal apoptosis after TBI and decreased the protein expression levels of caspase3 and Bax, increasing the levels of Bcl2. The levels of Tolllike receptor 2 (TLR2) and TLR4 were significantly decreased after CBL treatment. In TBI patients, CBL can also decrease TNFα, IL1ß, IL6, and NFκB levels. This result indicates that CBLmediated inhibition of neuroinflammation and apoptosis ameliorated neuronal death after TBI. The neuroprotective capacity of CBL is partly dependent on the TLR signaling pathway. Conclusions: Taken together, the results of this study indicate that CBL can improve neurological outcomes and reduce neuronal death against neuroinflammation and apoptosis via the TLR signaling pathway in mice.
Assuntos
Animais , Camundongos , Peptídeos/administração & dosagem , Espécies Reativas de Oxigênio/análise , Apoptose , Lesões Encefálicas Traumáticas/terapia , Doenças Neuroinflamatórias/veterináriaRESUMO
In mammals, the relationship between the immune system and behavior is widely studied. In fish, however, the knowledge concerning the brain immune response and behavioral changes during brain viral infection is very limited. To further investigate this subject, we used the model of tilapia lake virus (TiLV) infection of zebrafish (Danio rerio), which was previously developed in our laboratory. We demonstrated that TiLV persists in the brain of adult zebrafish for at least 90 days, even when the virus is not detectable in other peripheral organs. The virions were found in the whole brain. During TiLV infection, zebrafish displayed a clear sickness behavior: decreased locomotor activity, reduced food intake, and primarily localizes near the bottom zone of aquaria. Moreover, during swimming, individual fish exhibited also unusual spiral movement patterns. Gene expression study revealed that TiLV induces in the brain of adult fish strong antiviral and inflammatory response and upregulates expression of genes encoding microglia/macrophage markers. Finally, using zebrafish larvae, we showed that TiLV infection induces histopathological abnormalities in the brain and causes activation of the microglia which is manifested by changes in cell shape from a resting ramified state in mock-infected to a highly ameboid active state in TiLV-infected larvae. This is the first study presenting a comprehensive analysis of the brain immune response associated with microglia activation and subsequent sickness behavior during systemic viral infection in zebrafish.