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  1. Article ; Online: A Novel Automated Approach for Improving Standardization of the Marble Burying Test Enables Quantification of Burying Bouts and Activity Characteristics.

    Wahl, Lucas / Punt, A Mattijs / Arbab, Tara / Willuhn, Ingo / Elgersma, Ype / Badura, Aleksandra

    eNeuro

    2022  Volume 9, Issue 2

    Abstract: The marble burying test is a commonly used paradigm to describe phenotypes in mouse models of neurodevelopmental and psychiatric disorders. The current methodological approach relies predominantly on reporting the number of buried marbles at the end of ... ...

    Abstract The marble burying test is a commonly used paradigm to describe phenotypes in mouse models of neurodevelopmental and psychiatric disorders. The current methodological approach relies predominantly on reporting the number of buried marbles at the end of the test. By measuring the proxy of the behavior (buried marbles), many important characteristics regarding the temporal aspect of this assay are lost. Here, we introduce a novel, automated method to quantify mouse behavior during the marble burying test with the focus on the burying bouts and movement dynamics. Using open-source software packages, we trained a supervised machine learning algorithm (the "classifier") to distinguish burying behavior in freely moving mice. In order to confirm the classifier's accuracy and characterize burying events in high detail, we performed the marble burying test in three mouse models:
    MeSH term(s) Animals ; Behavior, Animal ; Calcium Carbonate ; Disease Models, Animal ; Humans ; Mice ; Nerve Tissue Proteins ; Obsessive-Compulsive Disorder ; Reference Standards
    Chemical Substances Nerve Tissue Proteins ; Sapap3 protein, mouse ; Shank2 protein, mouse ; Calcium Carbonate (H0G9379FGK)
    Language English
    Publishing date 2022-04-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2800598-3
    ISSN 2373-2822 ; 2373-2822
    ISSN (online) 2373-2822
    ISSN 2373-2822
    DOI 10.1523/ENEURO.0446-21.2022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The selective glucocorticoid receptor antagonist CORT125281 has tissue-specific activity.

    Koorneef, Lisa L / Kroon, Jan / Viho, Eva M G / Wahl, Lucas F / Heckmans, Kim M L / van Dorst, Marloes M A R / Hoekstra, Menno / Houtman, René / Hunt, Hazel / Meijer, Onno C

    The Journal of endocrinology

    2020  Volume 246, Issue 1, Page(s) 79–92

    Abstract: Glucocorticoids mediate numerous essential processes in the human body via binding to the glucocorticoid receptor (GR). Excessive GR signaling can cause disease, and GR antagonists can be used to treat many symptoms of glucocorticoid-induced pathology. ... ...

    Abstract Glucocorticoids mediate numerous essential processes in the human body via binding to the glucocorticoid receptor (GR). Excessive GR signaling can cause disease, and GR antagonists can be used to treat many symptoms of glucocorticoid-induced pathology. The purpose of this study was to characterize the tissue-specific properties of the selective GR antagonist CORT125281. We evaluated the antagonistic effects of CORT125281 upon acute and subchronic corticosterone exposure in mice. In the acute corticosterone setting, hypothalamus-pituitary-adrenal-axis activity was investigated by measurement of basal- and stress-induced corticosterone levels, adrenocorticotropic hormone levels and pituitary proopiomelanocortin expression. GR signaling was evaluated by RT-PCR analysis of GR-responsive transcripts in liver, muscle, brown adipose tissue (BAT), white adipose tissue (WAT) and hippocampus. Pretreatment with a high dose of CORT125281 antagonized GR activity in a tissue-dependent manner. We observed complete inhibition of GR-induced target gene expression in the liver, partial blockade in muscle and BAT and no antagonism in WAT and hippocampus. Tissue distribution only partially explained the lack of effective antagonism. CORT125281 treatment did not disinhibit the hypothalamus-pituitary-adrenal neuroendocrine axis. In the subchronic corticosterone setting, CORT125281 partially prevented corticosterone-induced hyperinsulinemia, but not hyperlipidemia and immune suppression. In conclusion, CORT125281 antagonizes GR transcriptional activity in a tissue-dependent manner and improves corticosterone-induced hyperinsulinemia. Tailored dosing of CORT125281 may allow tissue-specific inhibition of GR transcriptional activity.
    MeSH term(s) Adipose Tissue, Brown/drug effects ; Adipose Tissue, Brown/metabolism ; Adipose Tissue, White/drug effects ; Adipose Tissue, White/metabolism ; Animals ; Corticosterone/pharmacology ; Hippocampus/drug effects ; Hippocampus/metabolism ; Hyperinsulinism/chemically induced ; Hyperinsulinism/prevention & control ; Hyperlipidemias/metabolism ; Hyperlipidemias/prevention & control ; Hypothalamo-Hypophyseal System/drug effects ; Hypothalamo-Hypophyseal System/metabolism ; Liver/drug effects ; Liver/metabolism ; Mice ; Mifepristone/pharmacology ; Muscles/drug effects ; Muscles/metabolism ; Pituitary-Adrenal System/drug effects ; Pituitary-Adrenal System/metabolism ; Receptors, Glucocorticoid/antagonists & inhibitors ; Receptors, Glucocorticoid/metabolism
    Chemical Substances Receptors, Glucocorticoid ; Mifepristone (320T6RNW1F) ; Corticosterone (W980KJ009P)
    Language English
    Publishing date 2020-05-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3028-4
    ISSN 1479-6805 ; 0022-0795
    ISSN (online) 1479-6805
    ISSN 0022-0795
    DOI 10.1530/JOE-19-0486
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Activated PI3Kδ syndrome, an immunodeficiency disorder, leads to sensorimotor deficits recapitulated in a murine model.

    Serra, Ines / Manusama, Olivia R / Kaiser, Fabian M P / Floriano, Izi Izumi / Wahl, Lucas / van der Zalm, Christian / IJspeert, Hanna / van Hagen, P Martin / van Beveren, Nico J M / Arend, Sandra M / Okkenhaug, Klaus / Pel, Johan J M / Dalm, Virgil A S H / Badura, Aleksandra

    Brain, behavior, & immunity - health

    2021  Volume 18, Page(s) 100377

    Abstract: The phosphoinositide-3-kinase (PI3K) family plays a major role in cell signaling and is predominant in leukocytes. Gain-of-function (GOF) mutations in ... ...

    Abstract The phosphoinositide-3-kinase (PI3K) family plays a major role in cell signaling and is predominant in leukocytes. Gain-of-function (GOF) mutations in the
    Language English
    Publishing date 2021-10-19
    Publishing country United States
    Document type Journal Article
    ISSN 2666-3546
    ISSN (online) 2666-3546
    DOI 10.1016/j.bbih.2021.100377
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Biallelic PAX5 mutations cause hypogammaglobulinemia, sensorimotor deficits, and autism spectrum disorder.

    Kaiser, Fabian M P / Gruenbacher, Sarah / Oyaga, Maria Roa / Nio, Enzo / Jaritz, Markus / Sun, Qiong / van der Zwaag, Wietske / Kreidl, Emanuel / Zopf, Lydia M / Dalm, Virgil A S H / Pel, Johan / Gaiser, Carolin / van der Vliet, Rick / Wahl, Lucas / Rietman, André / Hill, Louisa / Leca, Ines / Driessen, Gertjan / Laffeber, Charlie /
    Brooks, Alice / Katsikis, Peter D / Lebbink, Joyce H G / Tachibana, Kikuë / van der Burg, Mirjam / De Zeeuw, Chris I / Badura, Aleksandra / Busslinger, Meinrad

    The Journal of experimental medicine

    2022  Volume 219, Issue 9

    Abstract: The genetic causes of primary antibody deficiencies and autism spectrum disorder (ASD) are largely unknown. Here, we report a patient with hypogammaglobulinemia and ASD who carries biallelic mutations in the transcription factor PAX5. A patient-specific ... ...

    Abstract The genetic causes of primary antibody deficiencies and autism spectrum disorder (ASD) are largely unknown. Here, we report a patient with hypogammaglobulinemia and ASD who carries biallelic mutations in the transcription factor PAX5. A patient-specific Pax5 mutant mouse revealed an early B cell developmental block and impaired immune responses as the cause of hypogammaglobulinemia. Pax5 mutant mice displayed behavioral deficits in all ASD domains. The patient and the mouse model showed aberrant cerebellar foliation and severely impaired sensorimotor learning. PAX5 deficiency also caused profound hypoplasia of the substantia nigra and ventral tegmental area due to loss of GABAergic neurons, thus affecting two midbrain hubs, controlling motor function and reward processing, respectively. Heterozygous Pax5 mutant mice exhibited similar anatomic and behavioral abnormalities. Lineage tracing identified Pax5 as a crucial regulator of cerebellar morphogenesis and midbrain GABAergic neurogenesis. These findings reveal new roles of Pax5 in brain development and unravel the underlying mechanism of a novel immunological and neurodevelopmental syndrome.
    MeSH term(s) Agammaglobulinemia ; Animals ; Autism Spectrum Disorder/genetics ; Heterozygote ; Mice ; Mutation/genetics ; PAX5 Transcription Factor/genetics
    Chemical Substances PAX5 Transcription Factor
    Language English
    Publishing date 2022-08-10
    Publishing country United States
    Document type Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20220498
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Correction: Biallelic PAX5 mutations cause hypogammaglobulinemia, sensorimotor deficits, and autism spectrum disorder.

    Kaiser, Fabian M P / Gruenbacher, Sarah / Oyaga, Maria Roa / Nio, Enzo / Jaritz, Markus / Sun, Qiong / van der Zwaag, Wietske / Kreidl, Emanuel / Zopf, Lydia M / Dalm, Virgil A S H / Pel, Johan / Gaiser, Carolin / van der Vliet, Rick / Wahl, Lucas / Rietman, André / Hill, Louisa / Leca, Ines / Driessen, Gertjan / Laffeber, Charlie /
    Brooks, Alice / Katsikis, Peter D / Lebbink, Joyce H G / Tachibana, Kikuë / van der Burg, Mirjam / De Zeeuw, Chris I / Badura, Aleksandra / Busslinger, Meinrad

    The Journal of experimental medicine

    2022  Volume 220, Issue 1

    Language English
    Publishing date 2022-12-07
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.2022049812012022c
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Treatment of anal fistula with Baccharis dracunculifolia extract. Experimental study in rats.

    Santos, Carlos Henrique Marques Dos / Cavasana, Antonio Luís / Moreira, Davyson de Lima / Dourado, Doroty Mesquita / Guimarães, Felipe Dos Santos / Barros, Fernanda Helene Reis / Campos, Gattass Carneiro Orro de / Leme, Guilherme Apolinário Laureano / Silva, Lucas Dutra Madrid da / Wahl, Lucas Marques / Gutterres, Nathália Barreto de Almeida / Matias, Rosemary / Câmara, Sara Jéssica Falcão / Santos, Sandro Endrick de Oliveira

    Revista do Colegio Brasileiro de Cirurgioes

    2020  Volume 46, Issue 5, Page(s) e20192297

    Abstract: Objective: to evaluate the efficacy of Baccharis dracunculifolia extract in the treatment of anal fistulas in rats.: Methods: twenty male Wistar rats were submitted to anal fistula and, after 30 days, were divided into three groups: Control Group, ... ...

    Title translation Tratamento da fístula anal com extrato de Baccharis dracunculifolia. Estudo experimental em ratos.
    Abstract Objective: to evaluate the efficacy of Baccharis dracunculifolia extract in the treatment of anal fistulas in rats.
    Methods: twenty male Wistar rats were submitted to anal fistula and, after 30 days, were divided into three groups: Control Group, with five animals; Carbopol Group, with five animals; and Baccharis dracunculifolia Group, with ten animals. In the Control Group, no treatment was performed. In the Carbopol Group, a daily infusion of Carbopol was performed for 30 days. In the Baccharis dracunculifolia Group, a daily infusion of Carbopol plus Baccharis dracunculifolia extract was performed for 30 days. Specimens were taken for histological analysis after euthanasia.
    Results: there was no complete closure of the fistulous tract in any of the animals. The mean area of the remaining tract was of 847.2µm2, 565.6µm2 and 372.7µm2, in the Control Group, Carbopol Group, and Baccharis dracunculifolia Group, respectively, (p=0.001). The mean of the inflammatory process score was of 2.4, 2.4, and 2.1, in the Control Group, Carbopol Group, and Baccharis dracunculifolia Group, respectively, (p=0.285), while the mean values of vascular congestion were of 1.6, 1.4, and 1.1, in the Control Group, Carbopol Group, and Baccharis dracunculifolia Group, respectively, (p=0.031).
    Conclusion: Baccharis dracunculifolia extract was able to reduce the lumen of the fistulous tracts and the degree of vascular congestion, without, however, reducing the local inflammatory process or totally closing the fistulous tracts.
    MeSH term(s) Animals ; Baccharis ; Disease Models, Animal ; Male ; Plant Extracts/pharmacology ; Plants, Medicinal ; Rats ; Rats, Wistar ; Rectal Fistula/pathology ; Rectal Fistula/rehabilitation
    Chemical Substances Plant Extracts
    Language English
    Publishing date 2020-01-17
    Publishing country Brazil
    Document type Journal Article
    ZDB-ID 2223714-8
    ISSN 1809-4546 ; 1809-4546
    ISSN (online) 1809-4546
    ISSN 1809-4546
    DOI 10.1590/0100-6991e-20192297
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Effectiveness of the Aloe Vera extract in the treatment of fistula-in-ano

    Cavasana, Antonio Luis / Santos, Carlos Henrique Marques dos / Dourado, Doroty Mesquita / Guimarães, Felipe dos Santos / Barros, Fernanda Helene Reis / de Campos, Gattass Carneiro Orro / Leme, Guilherme Apolinário Laureano / Silva, Lucas Dutra Madrid da / Wahl, Lucas Marques / Gutterres, Nathália Barreto de Almeida / Matias, Rosemary / Câmara, Sara Jéssica Falcão / Santos, Sandro Endrick de Oliveira

    Journal of Coloproctology

    2020  Volume 40, Issue 01, Page(s) 67–72

    Abstract: Rationale: Considering that anal fistulae are still challenging regarding their treatment due to the risk of fecal incontinence in the most complex cases and the increasing use of phytotherapeutic drugs such as Aloe Vera in medicine, even with proven ... ...

    Abstract Rationale: Considering that anal fistulae are still challenging regarding their treatment due to the risk of fecal incontinence in the most complex cases and the increasing use of phytotherapeutic drugs such as Aloe Vera in medicine, even with proven healing effectiveness, there is interest in researching this drug in the treatment of anal fistulae.
    Objective: To evaluate the efficacy of Aloe Vera extract in the treatment of anal fistulae in rats.
    Method: Thirty male Wistar rats weighing 250–300 g were submitted to anal fistula and after 30 days were divided into three groups: Control Group (GCo) (n = 5), Carbopol Group (GCa) (n = 5), and Aloe Vera Group (GAV) (n = 10). In the GCo no treatment was performed, while in the others a daily infusion of 0.3 mL of solution (Carbopol only in GCa and Carbopol plus Aloe Vera extract in the GAV) was performed through the external orifice of the fistula for 30 days. Afterwards, euthanasia was performed and specimens were removed for histological study. It was evaluated the closure of the fistulous tract, the area of the remaining tract, the inflammatory infiltrate and the degree of vascular congestion. The results were submitted to statistical treatment by Kruskall–Wallis test, considering p < 0.05.
    Results: There was no complete closure of the fistulous tract in any of the animals. The mean area of the remaining tract was 847.2 μm in the GCo, 565.6 μm in the GCa and 377.8 μm in the GAV (p < 0.05). The mean of the inflammatory infiltrate score was 2.4 in the GCo, 2.4 in the GCa and 2.3 in the GAV (p > 0.05), while in the evaluation of vascular congestion, we observed a mean of 1.6 in the GCo, 1.4 in GCa and 1.1 in GAV (p < 0.05).
    Conclusion: The extract of Aloe vera was able to reduce the lumen of the fistulous tract and reduce the degree of vascular congestion; however, it did not allow the complete closure of the fistulous tract nor diminished the inflammatory process.
    Keywords Rats ; Rectal fistula ; Phytotherapeutic drugs ; Atos ; Fístula retal ; Drogas fitoterapêuticas
    Language English
    Publishing date 2020-03-01
    Publisher Thieme Revinter Publicações Ltda.
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 2664477-0
    ISSN 2317-6423 ; 2237-9363 ; 2317-6423
    ISSN (online) 2317-6423
    ISSN 2237-9363 ; 2317-6423
    DOI 10.1016/j.jcol.2019.09.003
    Database Thieme publisher's database

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