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  1. Article ; Online: The circle of Willis revisited: Forebrain dehydration sensing facilitated by the anterior communicating artery: How hemodynamic properties facilitate more efficient dehydration sensing in amniotes.

    Fenrich, Matija / Habjanovic, Karlo / Kajan, Josip / Heffer, Marija

    BioEssays : news and reviews in molecular, cellular and developmental biology

    2020  Volume 43, Issue 2, Page(s) e2000115

    Abstract: We hypothesize that threat of dehydration provided selection pressure for the evolutionary emergence and persistence of the anterior communicating artery (ACoA - the inter-arterial connection that completes the Circle of Willis) in early amniotes. The ... ...

    Abstract We hypothesize that threat of dehydration provided selection pressure for the evolutionary emergence and persistence of the anterior communicating artery (ACoA - the inter-arterial connection that completes the Circle of Willis) in early amniotes. The ACoA is a hemodynamically insignificant artery, but, as we argue in this paper, its privileged position outside the blood-brain barrier gives it a crucial sensing function for the osmolarity of the blood against the background of the rest of the brain, which efficiently protects itself from dehydration. Till now, the questions of why the ACoA evolved, and what its physiological function is, have remained unsatisfactorily answered. The traditional view-that the ACoA serves as a collateral source of vascularization in case of arterial stenosis-is anthropocentric, and not in accordance with principles of natural selection that apply more generally. Diseases underlying arterial stenosis are associated with aging and the human lifestyle, so this cannot explain why the ACoA formed hundreds of millions of years ago and persisted in amniotes to this day. The peculiar hemodynamic properties of the ACoA could be selected traits that allowed for more efficient forebrain detection of dehydration and complex behavioral responses to water loss, a major advantage in the survival of early amniotes. This hypothesis also explains insufficient hydration often seen in elderly humans.
    MeSH term(s) Adult ; Aged ; Child ; Circle of Willis ; Dehydration ; Hemodynamics ; Humans ; Prosencephalon
    Language English
    Publishing date 2020-11-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.202000115
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  2. Article: SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury.

    Fenrich, Matija / Mrdenovic, Stefan / Balog, Marta / Tomic, Svetlana / Zjalic, Milorad / Roncevic, Alen / Mandic, Dario / Debeljak, Zeljko / Heffer, Marija

    Frontiers in cellular neuroscience

    2020  Volume 14, Page(s) 229

    Abstract: Coronavirus disease (CoVID-19), caused by recently identified severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), is characterized by inconsistent clinical presentations. While many infected individuals remain asymptomatic or show mild ...

    Abstract Coronavirus disease (CoVID-19), caused by recently identified severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), is characterized by inconsistent clinical presentations. While many infected individuals remain asymptomatic or show mild respiratory symptoms, others develop severe pneumonia or even respiratory distress syndrome. SARS-CoV-2 is reported to be able to infect the lungs, the intestines, blood vessels, the bile ducts, the conjunctiva, macrophages, T lymphocytes, the heart, liver, kidneys, and brain. More than a third of cases displayed neurological involvement, and many severely ill patients developed multiple organ infection and injury. However, less than 1% of patients had a detectable level of SARS-CoV-2 in the blood, raising a question of how the virus spreads throughout the body. We propose that nerve terminals in the orofacial mucosa, eyes, and olfactory neuroepithelium act as entry points for the brain invasion, allowing SARS-CoV-2 to infect the brainstem. By exploiting the subcellular membrane compartments of infected cells, a feature common to all coronaviruses, SARS-CoV-2 is capable to disseminate from the brain to periphery via vesicular axonal transport and passive diffusion through axonal endoplasmic reticula, causing multiple organ injury independently of an underlying respiratory infection. The proposed model clarifies a wide range of clinically observed phenomena in CoVID-19 patients, such as neurological symptoms unassociated with lung pathology, protracted presence of the virus in samples obtained from recovered patients, exaggerated immune response, and multiple organ failure in severe cases with variable course and dynamics of the disease. We believe that this model can provide novel insights into CoVID-19 and its long-term sequelae, and establish a framework for further research.
    Keywords covid19
    Language English
    Publishing date 2020-08-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2020.00229
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  3. Article ; Online: SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury

    Fenrich, Matija / Mrdenovic, Stefan / Balog, Marta / Tomic, Svetlana / Zjalic, Milorad / Roncevic, Alen / Mandic, Dario / Debeljak, Zeljko / Heffer, Marija

    Frontiers in Cellular Neuroscience

    2020  Volume 14

    Keywords Cellular and Molecular Neuroscience ; covid19
    Publisher Frontiers Media SA
    Publishing country ch
    Document type Article ; Online
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2020.00229
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  4. Article ; Online: SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury

    Matija Fenrich / Stefan Mrdenovic / Marta Balog / Svetlana Tomic / Milorad Zjalic / Alen Roncevic / Dario Mandic / Zeljko Debeljak / Marija Heffer

    Frontiers in Cellular Neuroscience, Vol

    2020  Volume 14

    Abstract: Coronavirus disease (CoVID-19), caused by recently identified severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), is characterized by inconsistent clinical presentations. While many infected individuals remain asymptomatic or show mild ...

    Abstract Coronavirus disease (CoVID-19), caused by recently identified severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), is characterized by inconsistent clinical presentations. While many infected individuals remain asymptomatic or show mild respiratory symptoms, others develop severe pneumonia or even respiratory distress syndrome. SARS-CoV-2 is reported to be able to infect the lungs, the intestines, blood vessels, the bile ducts, the conjunctiva, macrophages, T lymphocytes, the heart, liver, kidneys, and brain. More than a third of cases displayed neurological involvement, and many severely ill patients developed multiple organ infection and injury. However, less than 1% of patients had a detectable level of SARS-CoV-2 in the blood, raising a question of how the virus spreads throughout the body. We propose that nerve terminals in the orofacial mucosa, eyes, and olfactory neuroepithelium act as entry points for the brain invasion, allowing SARS-CoV-2 to infect the brainstem. By exploiting the subcellular membrane compartments of infected cells, a feature common to all coronaviruses, SARS-CoV-2 is capable to disseminate from the brain to periphery via vesicular axonal transport and passive diffusion through axonal endoplasmic reticula, causing multiple organ injury independently of an underlying respiratory infection. The proposed model clarifies a wide range of clinically observed phenomena in CoVID-19 patients, such as neurological symptoms unassociated with lung pathology, protracted presence of the virus in samples obtained from recovered patients, exaggerated immune response, and multiple organ failure in severe cases with variable course and dynamics of the disease. We believe that this model can provide novel insights into CoVID-19 and its long-term sequelae, and establish a framework for further research.
    Keywords SARS-CoV-2 ; neurotropic infection ; axonal transport ; peripheral nerves ; neurological symptoms ; multiple organ failure ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; covid19
    Subject code 610
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Book ; Online: Table_1_SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury.docx

    Matija Fenrich / Stefan Mrdenovic / Marta Balog / Svetlana Tomic / Milorad Zjalic / Alen Roncevic / Dario Mandic / Zeljko Debeljak / Marija Heffer

    2020  

    Abstract: Coronavirus disease (CoVID-19), caused by recently identified severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), is characterized by inconsistent clinical presentations. While many infected individuals remain asymptomatic or show mild ...

    Abstract Coronavirus disease (CoVID-19), caused by recently identified severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), is characterized by inconsistent clinical presentations. While many infected individuals remain asymptomatic or show mild respiratory symptoms, others develop severe pneumonia or even respiratory distress syndrome. SARS-CoV-2 is reported to be able to infect the lungs, the intestines, blood vessels, the bile ducts, the conjunctiva, macrophages, T lymphocytes, the heart, liver, kidneys, and brain. More than a third of cases displayed neurological involvement, and many severely ill patients developed multiple organ infection and injury. However, less than 1% of patients had a detectable level of SARS-CoV-2 in the blood, raising a question of how the virus spreads throughout the body. We propose that nerve terminals in the orofacial mucosa, eyes, and olfactory neuroepithelium act as entry points for the brain invasion, allowing SARS-CoV-2 to infect the brainstem. By exploiting the subcellular membrane compartments of infected cells, a feature common to all coronaviruses, SARS-CoV-2 is capable to disseminate from the brain to periphery via vesicular axonal transport and passive diffusion through axonal endoplasmic reticula, causing multiple organ injury independently of an underlying respiratory infection. The proposed model clarifies a wide range of clinically observed phenomena in CoVID-19 patients, such as neurological symptoms unassociated with lung pathology, protracted presence of the virus in samples obtained from recovered patients, exaggerated immune response, and multiple organ failure in severe cases with variable course and dynamics of the disease. We believe that this model can provide novel insights into CoVID-19 and its long-term sequelae, and establish a framework for further research.
    Keywords Cell Biology ; Neuroscience ; Cellular Nervous System ; Central Nervous System ; Cellular Interactions (incl. Adhesion ; Matrix ; Cell Wall) ; Protein Trafficking ; SARS-CoV-2 ; neurotropic infection ; axonal transport ; peripheral nerves ; neurological symptoms ; multiple organ failure ; covid19
    Subject code 610
    Publishing date 2020-08-05T04:22:49Z
    Publishing country uk
    Document type Book ; Online
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  6. Article: Elderly rats fed with a high-fat high-sucrose diet developed sex-dependent metabolic syndrome regardless of long-term metformin and liraglutide treatment.

    Ivić, Vedrana / Zjalić, Milorad / Blažetić, Senka / Fenrich, Matija / Labak, Irena / Scitovski, Rudolf / Szűcs, Kálmán Ferenc / Ducza, Eszter / Tábi, Tamás / Bagamery, Fruzsina / Szökő, Éva / Vuković, Rosemary / Rončević, Alen / Mandić, Dario / Debeljak, Željko / Berecki, Monika / Balog, Marta / Seres-Bokor, Adrienn / Sztojkov-Ivanov, Anita /
    Hajagos-Tóth, Judit / Gajović, Srećko / Imširović, Alen / Bakula, Marina / Mahiiovych, Solomiia / Gaspar, Robert / Vari, Sandor G / Heffer, Marija

    Frontiers in endocrinology

    2023  Volume 14, Page(s) 1181064

    Abstract: Aim/introduction: The study aimed to determine the effectiveness of early antidiabetic therapy in reversing metabolic changes caused by high-fat and high-sucrose diet (HFHSD) in both sexes.: Methods: Elderly Sprague-Dawley rats, 45 weeks old, were ... ...

    Abstract Aim/introduction: The study aimed to determine the effectiveness of early antidiabetic therapy in reversing metabolic changes caused by high-fat and high-sucrose diet (HFHSD) in both sexes.
    Methods: Elderly Sprague-Dawley rats, 45 weeks old, were randomized into four groups: a control group fed on the standard diet (STD), one group fed the HFHSD, and two groups fed the HFHSD along with long-term treatment of either metformin (HFHSD+M) or liraglutide (HFHSD+L). Antidiabetic treatment started 5 weeks after the introduction of the diet and lasted 13 weeks until the animals were 64 weeks old.
    Results: Unexpectedly, HFHSD-fed animals did not gain weight but underwent significant metabolic changes. Both antidiabetic treatments produced sex-specific effects, but neither prevented the onset of prediabetes nor diabetes.
    Conclusion: Liraglutide vested benefits to liver and skeletal muscle tissue in males but induced signs of insulin resistance in females.
    MeSH term(s) Animals ; Female ; Male ; Rats ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/therapeutic use ; Liraglutide/therapeutic use ; Metabolic Syndrome/drug therapy ; Metabolic Syndrome/etiology ; Metformin/therapeutic use ; Rats, Sprague-Dawley ; Sucrose/adverse effects ; Sex Factors
    Chemical Substances Hypoglycemic Agents ; Liraglutide (839I73S42A) ; Metformin (9100L32L2N) ; Sucrose (57-50-1)
    Language English
    Publishing date 2023-10-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2023.1181064
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  7. Article ; Online: Effect of different combination of maternal and postnatal diet on adipose tissue morphology in male rat offspring.

    Šnajder, Darija / Perić Kačarević, Željka / Grgić, Anđela / Bijelić, Nikola / Fenrich, Matija / Belovari, Tatjana / Radić, Radivoje

    The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians

    2018  Volume 32, Issue 11, Page(s) 1838–1846

    Abstract: Purpose: Adipose tissue expansion can occur through several different ways and, under certain conditions, can be connected with chronic inflammation. TNF-α is one of the important cytokines involved in this process. Prolonged inflammation in obesity can ...

    Abstract Purpose: Adipose tissue expansion can occur through several different ways and, under certain conditions, can be connected with chronic inflammation. TNF-α is one of the important cytokines involved in this process. Prolonged inflammation in obesity can lead to obesity-related insulin resistance and tissue dysfunction. The aim of our study was to investigate how different combination of maternal and postnatal diet affects offspring adipose tissue morphology and adipose tissue TNF-α expression.
    Methods: Ten female Sprague Dawley rats, 9 weeks old, were randomly divided into two groups and fed either standard laboratory chow or food rich in saturated fatty acids during 6 weeks and then mated with the same male rat. After birth and lactation male rat offspring from both groups were divided into four subgroups depending on the diet they were fed until 22 weeks old. Samples of white adipose tissue were taken from the subcutaneous, epididymal, and perirenal fat pad. On tissue sections, histomorphometric analysis was conducted using CellProfiler program v 2.1.1, and immunohistochemical staining for TNF-α was performed.
    Results: Greater mean surface area of subcutaneous and epididymal adipocytes was found in groups of male rat offspring with altered diet. In perirenal adipose tissue, the highest number of adipocytes was measured in the group where both mother and offspring were fed a high-fat diet. Adipocyte staining intensity for TNF-α did not differ significantly between the groups.
    Conclusions: Together with our previously published data, our results lead to the conclusion that alteration of postnatal diet can lead to TNF-α and adipocyte morphology changes.
    MeSH term(s) Adipose Tissue/cytology ; Adipose Tissue/metabolism ; Adiposity ; Animals ; Diet ; Female ; Male ; Pregnancy ; Prenatal Exposure Delayed Effects ; Prenatal Nutritional Physiological Phenomena ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2018-01-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2077261-0
    ISSN 1476-4954 ; 1057-0802 ; 1476-7058
    ISSN (online) 1476-4954
    ISSN 1057-0802 ; 1476-7058
    DOI 10.1080/14767058.2017.1419181
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  8. Article: SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury

    Fenrich, Matija / Mrdenovic, Stefan / Balog, Marta / Tomic, Svetlana / Zjalic, Milorad / Roncevic, Alen / Mandic, Dario / Debeljak, Zeljko / Heffer, Marija

    Front. Cell. Neurosci.

    Abstract: Coronavirus disease (CoVID-19), caused by recently identified severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), is characterized by inconsistent clinical presentations. While many infected individuals remain asymptomatic or show mild ...

    Abstract Coronavirus disease (CoVID-19), caused by recently identified severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), is characterized by inconsistent clinical presentations. While many infected individuals remain asymptomatic or show mild respiratory symptoms, others develop severe pneumonia or even respiratory distress syndrome. SARS-CoV-2 is reported to be able to infect the lungs, the intestines, blood vessels, the bile ducts, the conjunctiva, macrophages, T lymphocytes, the heart, liver, kidneys, and brain. More than a third of cases displayed neurological involvement, and many severely ill patients developed multiple organ infection and injury. However, less than 1% of patients had a detectable level of SARS-CoV-2 in the blood, raising a question of how the virus spreads throughout the body. We propose that nerve terminals in the orofacial mucosa, eyes, and olfactory neuroepithelium act as entry points for the brain invasion, allowing SARS-CoV-2 to infect the brainstem. By exploiting the subcellular membrane compartments of infected cells, a feature common to all coronaviruses, SARS-CoV-2 is capable to disseminate from the brain to periphery via vesicular axonal transport and passive diffusion through axonal endoplasmic reticula, causing multiple organ injury independently of an underlying respiratory infection. The proposed model clarifies a wide range of clinically observed phenomena in CoVID-19 patients, such as neurological symptoms unassociated with lung pathology, protracted presence of the virus in samples obtained from recovered patients, exaggerated immune response, and multiple organ failure in severe cases with variable course and dynamics of the disease. We believe that this model can provide novel insights into CoVID-19 and its long-term sequelae, and establish a framework for further research.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #732871
    Database COVID19

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