scholarly journals Recent advances in understanding Japanese encephalitis

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1915 ◽  
Author(s):  
Arup Banerjee ◽  
Aarti Tripathi
Keyword(s):  
Japanese Encephalitis ◽  
Microglial Activation ◽  
Brain Inflammation ◽  
Neurological Damage ◽  
Virus Structure ◽  
Recent Advances ◽  
Inflammatory Processes ◽  
Heavy Burden ◽  
Neuro Inflammation ◽  
The Brain

Japanese encephalitis (JE) is a clinical manifestation of the brain inflammation caused by JE virus (JEV). This virus imparts permanent neurological damage, thus imposing a heavy burden on public health and society. Neuro-inflammation is the hallmark of JEV infection. The prolonged pro-inflammatory response is due primarily to microglial activation, which eventually leads to severe encephalitis. A continual effort is going on in the scientific community toward an understanding of cellular and molecular factors that are involved in JEV neuro-invasion and inflammatory processes. This review not only gives a comprehensive update on the recent advances on understanding virus structure and mechanisms of pathogenesis but also briefly discusses crucial unresolved issues. We also highlight challenging areas of research that might open new avenues for controlling virus-induced neuro-inflammation.

scholarly journals Autophagy Inhibitors Treatment Alleviates Degree of Infection and Cerebral Inflammatory Responses in Mouse Model of Japanese Encephalitis

2021 ◽  
Author(s):  
Jinhua Zhang ◽  
Wei Han ◽  
changqing xie ◽  
mingxing Gao ◽  
Xugang Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Viral Infection ◽  
Japanese Encephalitis ◽  
Host Response ◽  
Inflammatory Responses ◽  
Heart Diseases ◽  
Brain Inflammation ◽  
Specific Mechanism ◽  
Epidemic Disease ◽  
The Brain

Abstract Background: Japanese Encephalitis (JE) is a zoonotic natural epidemic disease caused by Japanese Encephalitis Virus (JEV) infection. Currently, there is no specific medicine for Japanese encephalitis. At present, autophagy regulating drugs have played an important role in the treatment of tumors, heart diseases and other diseases. We hope that by studying the effects of autophagy-regulating drugs on JEV infection and host response in mice, will provide effective clinical trials for autophagy-regulating drugs in the treatment of Japanese encephalitis and other viral infectious diseases. Methods: After establishing appropriate animal model. We observed the neurological symptoms of the mice and counted their survival rate. We compared the degree of viral infection in the brain of mice infected with JE virus. We compared the extent of neuroinflammatory responses in the brain of mice and explored the signaling processes involved in neuroinflammation.Results: We found autophagy inhibitors wortmannin (Wort) and chloroquine (CQ) alleviate degree of viral infection in the brain of JEV-infected mice. Autophagy inhibitors reduced the neuroinflammation in Mouse Model of Japanese encephalitis. We speculated that autophagy inhibitors may attenuate the activation of the PI3K/AKT/NF-kB pathway, thereby reducing the brain inflammation in mice, thereby protecting mice from JEV-induced death. This result is not significant enough, the specific mechanism still needs further study.Conclusions: Our study suggests that autophagy inhibitors wortmannin and chloroquine could reduce the degree of viral infection and inflammatory response in the brain of JEV infected mice, providing a clinical basis for the treatment of Japanese encephalitis.

scholarly journals Evidence of microglial activation in autism and its possible role in brain underconnectivity

2011 ◽  
Vol 7 (2-4) ◽  
pp. 205-213 ◽  
Author(s):  
Juan I. Rodriguez ◽  
Janet K. Kern
Keyword(s):  
Microglial Activation ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Extended Period ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Brain Inflammation ◽  
Synaptic Connections ◽  
Future Studies ◽  
The Brain

Evidence indicates that children with autism spectrum disorder (ASD) suffer from an ongoing neuroinflammatory process in different regions of the brain involving microglial activation. When microglia remain activated for an extended period, the production of mediators is sustained longer than usual and this increase in mediators contributes to loss of synaptic connections and neuronal cell death. Microglial activation can then result in a loss of connections or underconnectivity. Underconnectivity is reported in many studies in autism. One way to control neuroinflammation is to reduce or inhibit microglial activation. It is plausible that by reducing brain inflammation and microglial activation, the neurodestructive effects of chronic inflammation could be reduced and allow for improved developmental outcomes. Future studies that examine treatments that may reduce microglial activation and neuroinflammation, and ultimately help to mitigate symptoms in ASD, are warranted.

scholarly journals Lack of Interferon Regulatory Factor 8 Associated with Restricted IFN-gamma expression Augmented Japanese Encephalitis Virus Replication in the Mouse Brain

2021 ◽  
Author(s):  
Aarti Tripathi ◽  
Bhupendra Singh Rawat ◽  
Sankar Addya ◽  
Milan Surjit ◽  
Prafullakumar B. Tailor ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Immune Cells ◽  
Microglial Activation ◽  
Interferon Regulatory Factor ◽  
Encephalitis Virus ◽  
Regulatory Factor ◽  
Myeloid Lineage ◽  
The Brain

Interferon Regulatory Factor 8 (IRF8), a myeloid lineage transcription factor, emerges as an essential regulator for microglia activation. However, the precise role of IRF8 during Japanese encephalitis virus (JEV) infection in the brain remains elusive. Here we report that JEV infection enhances IRF8 expression in the infected mice brain. Comparative transcriptional profiling of whole-brain RNA analysis and validation by qRT-PCR reveals an impaired IFNγ and related gene expression in Irf8 knockout ( Irf8 -/- ) infected mice. Further, Ifnγ knockout ( Ifnγ -/- ) mice exhibit a reduced level of Irf8. Both Ifnγ -/- and Irf8 -/- mice exhibit significantly reduced levels of activated (CD11b + CD45 hi , CD11b + CD45 lo , Cd68, and CD86 ) and infiltrating immune cells (Ly6C + , CD4, and CD8) in the infected brain as compared to WT mice. However, a higher level of granulocyte cells (Ly6G + ) infiltration is evident in Irf8 -/- mice and the increased concentration of TNFα, IL6, MCP1 levels in the brain. Interestingly, neither Irf8 -/- nor Ifnγ -/- has conferred protection against lethal JEV challenge to mice and exhibits augmentation in JEV replication in the brain. The gain of function of Irf8 by overexpressing functional IRF8 in an IRF8 deficient cell line attenuates viral replication and enhances IFNγ production. Overall, we summarise that in the murine model of JEV encephalitis, IRF8 modulation affects JEV replication. We also evidence that lack of Irf8 affects immune cells abundance in circulation and the infected brain leading to a reduction in IFNγ level and increased viral load in the brain. Importance Microglial cells, the resident macrophages in the brain, play a vital role in Japanese encephalitis virus (JEV) pathogenesis. The deregulated activity of microglia can be lethal for the brain. Therefore, it is crucial to understand the regulators that drive microglia's phenotype changes and induce inflammation in the brain. Interferon regulatory factor 8 (IRF8) is a myeloid lineage transcription factor involved in microglial activation. However, the impact of IRF8 modulation on JEV replication remains elusive. Moreover, the pathways regulated by IRF8 to initiate and amplify pathological neuroinflammation are not well understood. Here, we demonstrated the effect of IRF8 modulation on JEV replication, microglial activation, and immune cells infiltration in the brain.

scholarly journals Development and characterization of an animal model of Japanese encephalitis virus infection in adolescent C57BL/6 mice

2021 ◽  
Author(s):  
Aarti Tripathi ◽  
Arup Banerjee ◽  
Sudhanshu Vrati
Keyword(s):  
Mouse Model ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Encephalitis Virus ◽  
Brain Inflammation ◽  
Japanese Encephalitis Virus Infection ◽  
Molecular Events ◽  
Tnf Α ◽  
The Brain

A mouse-adapted isolate of Japanese encephalitis virus (JEV), designated as JEV-S3, was generated by serially passaging the P20778 strain of the virus in 3-4 weeks old C57BL/6 mice. The blood-brain barrier leakage was evident in JEV-S3 infected mice, where viral antigens and RNA were consistently demonstrated in the brain and infiltration of activated immune cells as evidenced by an increased level of CD45+CD11b+ cell population. Histopathology studies showed the presence of perivascular cuffing, haemorrhage and necrotic foci in the virus-infected brain conforming to the pathological changes seen in the brain of JEV-infected patients. Mass spectrometry studies characterized the molecular events leading to brain inflammation in the infected mice. Notably, a significant induction of inflammatory cytokines such as IFN-γ, Il-6, TNF-α, and TGF-β was observed. Further, genome sequencing of the JEV-S3 isolate identified the mutations selected during the mouse passage of the virus. Overall, we present an in-depth characterization of a robust and reproducible mouse model of JEV infection. The JEV-S3 isolate will be a useful tool to screen antivirals and study the virus pathogenesis in the adolescent mouse model.

scholarly journals Autophagy Inhibitors Treatment Alleviates Degree of Infection and Cerebral Inflammatory Responses in Mouse Model of Japanese Encephalitis

2021 ◽  
Author(s):  
Jinhua Zhang ◽  
Wei Han ◽  
Changqing Xie ◽  
Mingxing Gao ◽  
Xugang Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Viral Infection ◽  
Japanese Encephalitis ◽  
Host Response ◽  
Inflammatory Responses ◽  
Heart Diseases ◽  
Brain Inflammation ◽  
Specific Mechanism ◽  
Epidemic Disease ◽  
The Brain

Abstract Background: Japanese Encephalitis (JE) is a zoonotic natural epidemic disease caused by Japanese Encephalitis Virus (JEV) infection. Currently, there is no specific medicine for Japanese encephalitis. At present, autophagy regulating drugs have played an important role in the treatment of tumors, heart diseases and other diseases. We hope that by studying the effects of autophagy-regulating drugs on JEV infection and host response in mice, will provide effective clinical trials for autophagy-regulating drugs in the treatment of Japanese encephalitis and other viral infectious diseases. Methods: After establishing appropriate animal model. We observed the neurological symptoms of the mice and counted their survival rate. We compared the degree of viral infection in the brain of mice infected with JE virus. We compared the extent of neuroinflammatory responses in the brain of mice and explored the signaling processes involved in neuroinflammation.Results: We found autophagy inhibitors wortmannin (Wort) and chloroquine (CQ) alleviate degree of viral infection in the brain of JEV-infected mice. Autophagy inhibitors reduced the neuroinflammation in Mouse Model of Japanese encephalitis. We speculated that autophagy inhibitors may attenuate the activation of the PI3K/AKT/NF-kB pathway, thereby reducing the brain inflammation in mice, thereby protecting mice from JEV-induced death. This result is not significant enough, the specific mechanism still needs further study.Conclusions: Our study suggests that autophagy inhibitors wortmannin and chloroquine could reduce the degree of viral infection and inflammatory response in the brain of JEV infected mice, providing a clinical basis for the treatment of Japanese encephalitis.

scholarly journals Crosstalk between Existential Phenomenological Psychotherapy and Neurological Sciences in Mood and Anxiety Disorders

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 340
Author(s):  
Lehel Balogh ◽  
Masaru Tanaka ◽  
Nóra Török ◽  
László Vécsei ◽  
Shigeru Taguchi
Keyword(s):  
Anxiety Disorders ◽  
Biological Treatment ◽  
Sense Of Self ◽  
Phenomenological Approach ◽  
Neurological Damage ◽  
Mood And Anxiety Disorders ◽  
New Interpretation ◽  
And Behavior ◽  
The Impact ◽  
The Brain

Psychotherapy is a comprehensive biological treatment modifying complex underlying cognitive, emotional, behavioral, and regulatory responses in the brain, leading patients with mental illness to a new interpretation of the sense of self and others. Psychotherapy is an art of science integrated with psychology and/or philosophy. Neurological sciences study the neurological basis of cognition, memory, and behavior as well as the impact of neurological damage and disease on these functions, and their treatment. Both psychotherapy and neurological sciences deal with the brain; nevertheless, they continue to stay polarized. Existential phenomenological psychotherapy (EPP) has been in the forefront of meaning-centered counseling for almost a century. The phenomenological approach in psychotherapy originated in the works of Martin Heidegger, Ludwig Binswanger, Medard Boss, and Viktor Frankl, and it has been committed to accounting for the existential possibilities and limitations of one’s life. EPP provides philosophically rich interpretations and empowers counseling techniques to assist mentally suffering individuals by finding meaning and purpose to life. The approach has proven to be effective in treating mood and anxiety disorders. This narrative review article demonstrates the development of EPP, the therapeutic methodology, evidence-based accounts of its curative techniques, current understanding of mood and anxiety disorders in neurological sciences, and a possible converging path to translate and integrate meaning-centered psychotherapy and neuroscience, concluding that the EPP may potentially play a synergistic role with the currently prevailing medication-based approaches for the treatment of mood and anxiety disorders.

scholarly journals PET evaluation of light-induced modulation of microglial activation and GLP-1R expression in depressive rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Liu ◽  
Lizhen Wang ◽  
Donghui Pan ◽  
Mingzhu Li ◽  
Yaoqi Li ◽  
...  
Keyword(s):  
Microglial Activation ◽  
Light Therapy ◽  
Emission Tomography ◽  
Noninvasive Evaluation ◽  
Mild Stress ◽  
Positron Emission ◽  
Therapeutic Choice ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain

AbstractLight therapy has been accepted as a promising therapeutic choice for depression. Positron emission tomography (PET) combined with specific radiotracers has great benefits for revealing pathogenesis and developing therapeutics. This study aimed to investigate the influences of light therapy on microglial activation and glucagon-like peptide-1 receptor (GLP-1R) expression in the brain of depressive rats using [18F]DPA-714 and [18F]exendin-4 PET. The results showed that chronic unpredictable mild stress (CUMS)-induced depressive rats had poorer performance in behavioral tests compared to normal rats (p < 0.05) and the depressive-like behavior could be ameliorated by light therapy. Besides, depressive rats had significantly higher [18F]DPA-714 uptake and lower [18F]FDG uptake compare to normal rats in 11 and 9 regions of interest (ROIs) of the brain, respectively (p < 0.05). After 5 weeks of light therapy, higher [18F]FDG and [18F]exendin-4 uptake was observed in most ROIs of light therapy-treated depressive rats compared to untreated depressive rats (p < 0.05) and no significant differences existed in [18F]DPA-714 uptake between the two groups. This study demonstrated that light therapy can ameliorate depressive-like behavior, improve glucose metabolism, and halt the decline of brain GLP-1R expression of depressive rats, but have no effects on microglial activation caused by CUMS. Besides, this study validated that [18F]DPA-714 and [18F]exendin-4 PET have the potential for noninvasive evaluation of microglial activation and GLP-1R expression in the brain of depression.

scholarly journals Cognitive impairments induced by necrotizing enterocolitis can be prevented by inhibiting microglial activation in mouse brain

2018 ◽  
Vol 10 (471) ◽  
pp. eaan0237 ◽  
Author(s):  
Diego F. Niño ◽  
Qinjie Zhou ◽  
Yukihiro Yamaguchi ◽  
Laura Y. Martin ◽  
Sanxia Wang ◽  
...  
Keyword(s):  
Necrotizing Enterocolitis ◽  
Microglial Activation ◽  
Gastrointestinal Disease ◽  
Cognitive Impairments ◽  
High Mobility ◽  
Neurological Dysfunction ◽  
Mucosal Inflammation ◽  
Signaling Axis ◽  
The Brain

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease of the premature infant. One of the most important long-term complications observed in children who survive NEC early in life is the development of profound neurological impairments. However, the pathways leading to NEC-associated neurological impairments remain unknown, thus limiting the development of prevention strategies. We have recently shown that NEC development is dependent on the expression of the lipopolysaccharide receptor Toll-like receptor 4 (TLR4) on the intestinal epithelium, whose activation by bacteria in the newborn gut leads to mucosal inflammation. Here, we hypothesized that damage-induced production of TLR4 endogenous ligands in the intestine might lead to activation of microglial cells in the brain and promote cognitive impairments. We identified a gut-brain signaling axis in an NEC mouse model in which activation of intestinal TLR4 signaling led to release of high-mobility group box 1 in the intestine that, in turn, promoted microglial activation in the brain and neurological dysfunction. We further demonstrated that an orally administered dendrimer-based nanotherapeutic approach to targeting activated microglia could prevent NEC-associated neurological dysfunction in neonatal mice. These findings shed light on the molecular pathways leading to the development of NEC-associated brain injury, provide a rationale for early removal of diseased intestine in NEC, and indicate the potential of targeted therapies that protect the developing brain in the treatment of NEC in early childhood.

Adenovirus in the brain: recent advances of gene therapy for neurodegenerative diseases

1998 ◽  
Vol 55 (4) ◽  
pp. 333-341 ◽  
Author(s):  
M. Barkats ◽  
A. Bilang-Bleuel ◽  
M.H. Buc-Caron ◽  
M.N. Castel-Barthe ◽  
O. Corti ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Neurodegenerative Diseases ◽  
Recent Advances ◽  
The Brain

scholarly journals Comparisons of neuroinflammation, microglial activation, and degeneration of the locus coeruleus-norepinephrine system in APP/PS1 and aging mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Song Cao ◽  
Daniel W. Fisher ◽  
Guadalupe Rodriguez ◽  
Tian Yu ◽  
Hongxin Dong
Keyword(s):  
Spinal Cord ◽  
Locus Coeruleus ◽  
Microglial Activation ◽  
Healthy Aging ◽  
Cell Types ◽  
Norepinephrine System ◽  
Protective Processes ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

Abstract Background The role of microglia in Alzheimer’s disease (AD) pathogenesis is becoming increasingly important, as activation of these cell types likely contributes to both pathological and protective processes associated with all phases of the disease. During early AD pathogenesis, one of the first areas of degeneration is the locus coeruleus (LC), which provides broad innervation of the central nervous system and facilitates norepinephrine (NE) transmission. Though the LC-NE is likely to influence microglial dynamics, it is unclear how these systems change with AD compared to otherwise healthy aging. Methods In this study, we evaluated the dynamic changes of neuroinflammation and neurodegeneration in the LC-NE system in the brain and spinal cord of APP/PS1 mice and aged WT mice using immunofluorescence and ELISA. Results Our results demonstrated increased expression of inflammatory cytokines and microglial activation observed in the cortex, hippocampus, and spinal cord of APP/PS1 compared to WT mice. LC-NE neuron and fiber loss as well as reduced norepinephrine transporter (NET) expression was more evident in APP/PS1 mice, although NE levels were similar between 12-month-old APP/PS1 and WT mice. Notably, the degree of microglial activation, LC-NE nerve fiber loss, and NET reduction in the brain and spinal cord were more severe in 12-month-old APP/PS1 compared to 12- and 24-month-old WT mice. Conclusion These results suggest that elevated neuroinflammation and microglial activation in the brain and spinal cord of APP/PS1 mice correlate with significant degeneration of the LC-NE system.

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