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  1. AU="Clarke, Julia R"
  2. AU=Jordan William D Jr
  3. AU="Frangaj, Brulinda"
  4. AU="Oostindjer, Andrew"
  5. AU="Diarra, Zoumana"
  6. AU="Saragoni, V G"

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  1. Artikel ; Online: Fundamental neurochemistry review: Glutamatergic dysfunction as a central mechanism underlying flavivirus-induced neurological damage.

    Nogueira, Clara O / Rocha, Tamires / Messor, Daniel F / Souza, Isis N O / Clarke, Julia R

    Journal of neurochemistry

    2023  Band 166, Heft 6, Seite(n) 915–927

    Abstract: The Flaviviridae family comprises positive-sense single-strand RNA viruses mainly transmitted by arthropods. Many of these pathogens are especially deleterious to the nervous system, and a myriad of neurological symptoms have been associated with ... ...

    Abstract The Flaviviridae family comprises positive-sense single-strand RNA viruses mainly transmitted by arthropods. Many of these pathogens are especially deleterious to the nervous system, and a myriad of neurological symptoms have been associated with infections by Zika virus (ZIKV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) in humans. Studies suggest that viral replication in neural cells and the massive release of pro-inflammatory mediators lead to morphological alterations of synaptic spine structure and changes in the balance of excitatory/inhibitory neurotransmitters and receptors. Glutamate is the predominant excitatory neurotransmitter in the brain, and studies propose that either enhanced release or impaired uptake of this amino acid contributes to brain damage in several conditions. Here, we review existing evidence suggesting that glutamatergic dysfunction-induced by flaviviruses is a central mechanism for neurological damage and clinical outcomes of infection. We also discuss current data suggesting that pharmacological approaches that counteract glutamatergic dysfunction show benefits in animal models of such viral diseases.
    Mesh-Begriff(e) Animals ; Humans ; Flavivirus ; Neurochemistry ; Zika Virus Infection ; Zika Virus ; Glutamic Acid
    Chemische Substanzen Glutamic Acid (3KX376GY7L)
    Sprache Englisch
    Erscheinungsdatum 2023-08-21
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/jnc.15935
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  2. Artikel ; Online: SARS-CoV-2-associated cytokine storm during pregnancy as a possible risk factor for neuropsychiatric disorder development in post-pandemic infants.

    Figueiredo, Claudia P / Fontes-Dantas, Fabrícia L / da Poian, Andrea T / Clarke, Julia R

    Neuropharmacology

    2021  Band 201, Seite(n) 108841

    Abstract: A strong association between perinatal viral infections and neurodevelopmental disorders has been established. Both the direct contact of the virus with the developing brain and the strong maternal immune response originated by viral infections can ... ...

    Abstract A strong association between perinatal viral infections and neurodevelopmental disorders has been established. Both the direct contact of the virus with the developing brain and the strong maternal immune response originated by viral infections can impair proper neurodevelopment. Coronavirus disease 2019 (COVID-19), caused by the highly-infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently responsible for a large global outbreak and is a major public health issue. While initial studies focused on the viral impact on the respiratory system, increasing evidence suggest that SARS-CoV-2 infects other organs and tissues including the mature brain. While studies continue to determine the neuropathology associated to COVID-19, the consequences of SARS-CoV-2 infection to the developing brain remain largely unexplored. The present review discusses evidence suggesting that SARS-CoV-2 infection may have persistent effects on the course of pregnancy and on brain development. Studies have shown that several proinflammatory mediators which are increased in the SARS-CoV-2-associated cytokine storm, are also modified in other viral infections known to increase the risk of neurodevelopmental disorders. In this sense, further studies should assess the genuine effects of SARS-CoV-2 infection during pregnancy and delivery along with an extended follow-up of the offspring, including neurocognitive, neuroimaging, and electrophysiological examination. It also remains to be determined whether and by which mechanisms SARS-CoV-2 intrauterine and early life infection could lead to an increased risk of developing neuropsychiatric disorders, such as autism (ASD) and schizophrenia (SZ), in the offspring.
    Mesh-Begriff(e) Autism Spectrum Disorder/epidemiology ; Autism Spectrum Disorder/immunology ; Brain/embryology ; Brain/immunology ; COVID-19/epidemiology ; COVID-19/immunology ; Cytokine Release Syndrome/epidemiology ; Cytokine Release Syndrome/immunology ; Female ; Humans ; Infectious Disease Transmission, Vertical ; Neurodevelopmental Disorders/epidemiology ; Neurodevelopmental Disorders/immunology ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology ; Pregnancy Complications, Infectious/immunology ; Prenatal Exposure Delayed Effects/epidemiology ; Prenatal Exposure Delayed Effects/immunology ; Risk Factors ; SARS-CoV-2 ; Schizophrenia/epidemiology ; Schizophrenia/immunology
    Sprache Englisch
    Erscheinungsdatum 2021-10-16
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 218272-5
    ISSN 1873-7064 ; 0028-3908
    ISSN (online) 1873-7064
    ISSN 0028-3908
    DOI 10.1016/j.neuropharm.2021.108841
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Dissociation of genotype-dependent cognitive and motor behavior in a strain of aging mice devoid of the prion protein.

    Janner, Daiane R / de Lima, Emanuelle V / da Silva, Rachel T / Clarke, Julia R / Linden, Rafael

    Behavioural brain research

    2021  Band 411, Seite(n) 113386

    Abstract: The prion glycoprotein ( ... ...

    Abstract The prion glycoprotein (PrP
    Mesh-Begriff(e) Age Factors ; Aging/metabolism ; Animals ; Animals, Outbred Strains ; Brain/metabolism ; Cognition/physiology ; Female ; Genotype ; Male ; Mice ; Mice, Knockout ; Motor Activity/genetics ; Motor Activity/physiology ; Prion Proteins/genetics ; Prion Proteins/metabolism ; Prions/genetics ; Prions/metabolism
    Chemische Substanzen Prion Proteins ; Prions ; Prnp protein, mouse
    Sprache Englisch
    Erscheinungsdatum 2021-05-27
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 449927-x
    ISSN 1872-7549 ; 0166-4328
    ISSN (online) 1872-7549
    ISSN 0166-4328
    DOI 10.1016/j.bbr.2021.113386
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  4. Artikel ; Online: Different outcomes of neonatal and adult Zika virus infection on startle reflex and prepulse inhibition in mice.

    Souza, Isis N O / Andrade, Brenda S / Frost, Paula S / Neris, Romulo L S / Gavino-Leopoldino, Daniel / Da Poian, Andrea T / Assunção-Miranda, Iranaia / Figueiredo, Claudia P / Clarke, Julia R / Neves, Gilda A

    Behavioural brain research

    2023  Band 451, Seite(n) 114519

    Abstract: Zika virus (ZIKV) infection causes severe neurological consequences in both gestationally-exposed infants and adults. Sensorial gating deficits strongly correlate to the motor, sensorial and cognitive impairments observed in ZIKV-infected patients. ... ...

    Abstract Zika virus (ZIKV) infection causes severe neurological consequences in both gestationally-exposed infants and adults. Sensorial gating deficits strongly correlate to the motor, sensorial and cognitive impairments observed in ZIKV-infected patients. However, no startle response or prepulse inhibition (PPI) assessment has been made in patients or animal models. In this study, we identified different outcomes according to the age of infection and sex in mice: neonatally infected animals presented an increase in PPI and delayed startle latency. However, adult-infected male mice presented lower startle amplitude, while a PPI impairment was observed 14 days after infection in both sexes. Our data further the understanding of the functional impacts of ZIKV on the developing and mature nervous system, which could help explain other behavioral and cognitive alterations caused by the virus. With this study, we support the startle reflex testing in ZIKV-exposed patients, especially infants, allowing for early detection of functional neuromotor damage and early intervention.
    Mesh-Begriff(e) Female ; Male ; Animals ; Mice ; Reflex, Startle/physiology ; Prepulse Inhibition ; Zika Virus ; Zika Virus Infection/complications ; Acoustic Stimulation
    Sprache Englisch
    Erscheinungsdatum 2023-05-31
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 449927-x
    ISSN 1872-7549 ; 0166-4328
    ISSN (online) 1872-7549
    ISSN 0166-4328
    DOI 10.1016/j.bbr.2023.114519
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  5. Artikel ; Online: Zika virus infection impairs synaptogenesis, induces neuroinflammation, and could be an environmental risk factor for autism spectrum disorder outcome.

    Ohki, Cristine Marie Yde / Benazzato, Cecília / van der Linden, Vanessa / França, Julia V / Toledo, Carmen M / Machado, Rafael Rahal Guaragna / Araujo, Danielle Bastos / Oliveira, Danielle Bruna Leal / Neris, Romulo S / Assunção-Miranda, Iranaia / de Oliveira Souza, Isis Nem / Nogueira, Clara O / Leite, Paulo Emilio Corrêa / van der Linden, Hélio / Figueiredo, Claudia P / Durigon, Edison Luiz / Clarke, Julia R / Russo, Fabiele Baldino / Beltrão-Braga, Patricia Cristina Baleeiro

    Biochimica et biophysica acta. Molecular basis of disease

    2024  Band 1870, Heft 5, Seite(n) 167097

    Abstract: Zika virus (ZIKV) infection was first associated with Central Nervous System (CNS) infections in Brazil in 2015, correlated with an increased number of newborns with microcephaly, which ended up characterizing the Congenital Zika Syndrome (CZS). Here, we ...

    Abstract Zika virus (ZIKV) infection was first associated with Central Nervous System (CNS) infections in Brazil in 2015, correlated with an increased number of newborns with microcephaly, which ended up characterizing the Congenital Zika Syndrome (CZS). Here, we investigated the impact of ZIKV infection on the functionality of iPSC-derived astrocytes. Besides, we extrapolated our findings to a Brazilian cohort of 136 CZS children and validated our results using a mouse model. Interestingly, ZIKV infection in neuroprogenitor cells compromises cell migration and causes apoptosis but does not interfere in astrocyte generation. Moreover, infected astrocytes lost their ability to uptake glutamate while expressing more glutamate transporters and secreted higher levels of IL-6. Besides, infected astrocytes secreted factors that impaired neuronal synaptogenesis. Since these biological endophenotypes were already related to Autism Spectrum Disorder (ASD), we extrapolated these results to a cohort of children, now 6-7 years old, and found seven children with ASD diagnosis (5.14 %). Additionally, mice infected by ZIKV revealed autistic-like behaviors, with a significant increase of IL-6 mRNA levels in the brain. Considering these evidence, we inferred that ZIKV infection during pregnancy might lead to synaptogenesis impairment and neuroinflammation, which could increase the risk for ASD.
    Sprache Englisch
    Erscheinungsdatum 2024-02-24
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article
    ZDB-ID 60-7
    ISSN 1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbadis.2024.167097
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  6. Artikel ; Online: Metabolic Dysfunction in Alzheimer's Disease: From Basic Neurobiology to Clinical Approaches.

    Clarke, Julia R / Ribeiro, Felipe C / Frozza, Rudimar L / De Felice, Fernanda G / Lourenco, Mychael V

    Journal of Alzheimer's disease : JAD

    2018  Band 64, Heft s1, Seite(n) S405–S426

    Abstract: Clinical trials have extensively failed to find effective treatments for Alzheimer's disease (AD) so far. Even after decades of AD research, there are still limited options for treating dementia. Mounting evidence has indicated that AD patients develop ... ...

    Abstract Clinical trials have extensively failed to find effective treatments for Alzheimer's disease (AD) so far. Even after decades of AD research, there are still limited options for treating dementia. Mounting evidence has indicated that AD patients develop central and peripheral metabolic dysfunction, and the underpinnings of such events have recently begun to emerge. Basic and preclinical studies have unveiled key pathophysiological mechanisms that include aberrant brain stress signaling, inflammation, and impaired insulin sensitivity. These findings are in accordance with clinical and neuropathological data suggesting that AD patients undergo central and peripheral metabolic deregulation. Here, we review recent basic and clinical findings indicating that metabolic defects are central to AD pathophysiology. We further propose a view for future therapeutics that incorporates metabolic defects as a core feature of AD pathogenesis. This approach could improve disease understanding and therapy development through drug repurposing and/or identification of novel metabolic targets.
    Mesh-Begriff(e) Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Animals ; Humans
    Sprache Englisch
    Erscheinungsdatum 2018-03-21
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-179911
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  7. Artikel ; Online: Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp

    Del Castilo, Ingrid / Neumann, Arthur S / Lemos, Felipe S / De Bastiani, Marco A / Oliveira, Felipe L / Zimmer, Eduardo R / Rêgo, Amanda M / Hardoim, Cristiane C P / Antunes, Luis Caetano M / Lara, Flávio A / Figueiredo, Claudia P / Clarke, Julia R

    International journal of molecular sciences

    2022  Band 23, Heft 10

    Abstract: ... ...

    Abstract RoundUp
    Mesh-Begriff(e) Adult ; Animals ; Dysbiosis/chemically induced ; Female ; Gastrointestinal Microbiome ; Glycine/analogs & derivatives ; Glycine/toxicity ; Herbicides/toxicity ; Humans ; Mice ; Pregnancy ; Glyphosate
    Chemische Substanzen Herbicides ; Glycine (TE7660XO1C)
    Sprache Englisch
    Erscheinungsdatum 2022-05-17
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23105583
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  8. Artikel ; Online: Consequences of gestational diabetes to the brain and behavior of the offspring.

    Sousa, Ricardo A L DE / Torres, Yasmin S / Figueiredo, Claudia P / Passos, Giselle F / Clarke, Julia R

    Anais da Academia Brasileira de Ciencias

    2017  Band 90, Heft 2 suppl 1, Seite(n) 2279–2291

    Abstract: Gestational diabetes mellitus (GD) is a form of insulin resistance triggered during the second/third trimesters of pregnancy in previously normoglycemic women. It is currently estimated that 10% of all pregnancies in the United States show this condition. ...

    Abstract Gestational diabetes mellitus (GD) is a form of insulin resistance triggered during the second/third trimesters of pregnancy in previously normoglycemic women. It is currently estimated that 10% of all pregnancies in the United States show this condition. For many years, the transient nature of GD has led researchers and physicians to assume that long-term consequences were absent. However, GD diagnosis leads to a six-fold increase in the risk of developing type 2 diabetes (T2D) in women and incidence of obesity and T2D is also higher among their infants. Recent and concerning evidences point to detrimental effects of GD on the behavior and cognition of the offspring, which often persist until adolescence or adulthood. Considering that the perinatal period is critical for determination of adult behavior, it is expected that the intra-uterine exposure to hyperglycemia, hyperinsulinemia and pro-inflammatory mediators, hallmark features of GD, might affect brain development. Here, we review early clinical and experimental evidence linking GD to consequences on the behavior of the offspring, focusing on memory and mood disorders. We also discuss initial evidence suggesting that downregulation of insulin signaling cascades are seen in the brains of GD offspring and could contribute to the consequences on their behavior.
    Mesh-Begriff(e) Animals ; Brain Chemistry ; Diabetes, Gestational ; Disease Models, Animal ; Female ; Insulin ; Memory Disorders/etiology ; Mental Disorders/etiology ; Neurodevelopmental Disorders/etiology ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats
    Chemische Substanzen Insulin
    Sprache Englisch
    Erscheinungsdatum 2017-08-14
    Erscheinungsland Brazil
    Dokumenttyp Journal Article
    ZDB-ID 2046885-4
    ISSN 1678-2690 ; 0001-3765
    ISSN (online) 1678-2690
    ISSN 0001-3765
    DOI 10.1590/0001-3765201720170264
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Mice lacking 5-lipoxygenase display motor deficits associated with cortical and hippocampal synapse abnormalities.

    Barbosa-Silva, Maria Carolina / P Campos, Raquel Maria / Del Castilo, Ingrid / França, Júlia V / Frost, Paula S / Penido, Carmen / Clarke, Julia R / Canetti, Claudio / Ribeiro-Resende, Victor T

    Brain, behavior, and immunity

    2021  Band 100, Seite(n) 183–193

    Abstract: Neural-immune interactions are related to the synapse plasticity and other dynamic processes in the nervous system. The absence or dysfunction of cellular/molecular elements from the immune system lead to impairments in the central and peripheral nervous ...

    Abstract Neural-immune interactions are related to the synapse plasticity and other dynamic processes in the nervous system. The absence or dysfunction of cellular/molecular elements from the immune system lead to impairments in the central and peripheral nervous system with behavior consequences such as cognitive, sensory, and locomotor deficits as well as social disabilities and anxiety disturbances. Cellular interactions between immune cells such as macrophages, microglia, and neutrophils with glial or neuronal cells have been of increasing interest over the last years. However, little is known about the role of immune-derived soluble factors in the context of homeostasis of the nervous system. Leukotrienes (LTs) are lipid mediators derived from the oxidation of arachidonic acid by 5-lipoxygenase (5-LO), and are classically involved in inflammation, allergies, and asthma. Here, we demonstrated that adult mice lacking 5-LO (5-LO
    Mesh-Begriff(e) Animals ; Arachidonate 5-Lipoxygenase/deficiency ; Arachidonate 5-Lipoxygenase/genetics ; Arachidonate 5-Lipoxygenase/metabolism ; Brain/metabolism ; CX3C Chemokine Receptor 1/biosynthesis ; Cerebral Cortex/metabolism ; Hippocampus/metabolism ; Mice ; Microglia/metabolism ; Motor Disorders/etiology ; Motor Disorders/metabolism ; Neurons/metabolism ; Synapses/metabolism
    Chemische Substanzen CX3C Chemokine Receptor 1 ; Cx3cr1 protein, mouse ; Arachidonate 5-Lipoxygenase (EC 1.13.11.34)
    Sprache Englisch
    Erscheinungsdatum 2021-12-08
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639219-2
    ISSN 1090-2139 ; 0889-1591
    ISSN (online) 1090-2139
    ISSN 0889-1591
    DOI 10.1016/j.bbi.2021.12.004
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  10. Artikel: Late Neurological Consequences of Zika Virus Infection: Risk Factors and Pharmaceutical Approaches.

    Souza, Isis N O / Barros-Aragão, Fernanda G Q / Frost, Paula S / Figueiredo, Claudia P / Clarke, Julia R

    Pharmaceuticals (Basel, Switzerland)

    2019  Band 12, Heft 2

    Abstract: Zika virus (ZIKV) infection was historically considered a disease with mild symptoms and no major consequences to human health. However, several long-term, late onset, and chronic neurological complications, both in congenitally-exposed babies and in ... ...

    Abstract Zika virus (ZIKV) infection was historically considered a disease with mild symptoms and no major consequences to human health. However, several long-term, late onset, and chronic neurological complications, both in congenitally-exposed babies and in adult patients, have been reported after ZIKV infection, especially after the 2015 epidemics in the American continent. The development or severity of these conditions cannot be fully predicted, but it is possible that genetic, epigenetic, and environmental factors may contribute to determine ZIKV infection outcomes. This reinforces the importance that individuals exposed to ZIKV are submitted to long-term clinical surveillance and highlights the urgent need for the development of therapeutic approaches to reduce or eliminate the neurological burden of infection. Here, we review the epidemiology of ZIKV-associated neurological complications and the role of factors that may influence disease outcome. Moreover, we discuss experimental and clinical evidence of drugs that have shown promising results in vitro or in vitro against viral replication and and/or ZIKV-induced neurotoxicity.
    Sprache Englisch
    Erscheinungsdatum 2019-04-17
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph12020060
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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