A5085527671- Autism Spectrum Disorder Research
- Genetics and Neurodevelopmental Disorders
- Immunodeficiency and Autoimmune Disorders
- CRISPR and Genetic Engineering
- Hormonal Regulation and Hypertension
- Neuroendocrine regulation and behavior
- Animal Genetics and Reproduction
- Stress Responses and Cortisol
- RNA modifications and cancer
- Congenital heart defects research
- Hearing, Cochlea, Tinnitus, Genetics
- Estrogen and related hormone effects
- Adipose Tissue and Metabolism
- Vestibular and auditory disorders
- Receptor Mechanisms and Signaling
- Genetic Neurodegenerative Diseases
- Neurobiology and Insect Physiology Research
- Zebrafish Biomedical Research Applications
- Medical and Biological Sciences
- Obsessive-Compulsive Spectrum Disorders
Erasmus University Rotterdam
2021-2024
Erasmus MC
2021-2024
Leiden University Medical Center
2020-2022
Rockefeller University
2022
The genetic causes of primary antibody deficiencies and autism spectrum disorder (ASD) are largely unknown. Here, we report a patient with hypogammaglobulinemia ASD who carries biallelic mutations in the transcription factor PAX5. A patient-specific Pax5 mutant mouse revealed an early B cell developmental block impaired immune responses as cause hypogammaglobulinemia. mice displayed behavioral deficits all domains. model showed aberrant cerebellar foliation severely sensorimotor learning....
Glucocorticoids mediate numerous essential processes in the human body via binding to glucocorticoid receptor (GR). Excessive GR signaling can cause disease, and antagonists be used treat many symptoms of glucocorticoid-induced pathology. The purpose this study was characterize tissue-specific properties selective antagonist CORT125281. We evaluated antagonistic effects CORT125281 upon acute subchronic corticosterone exposure mice. In setting, hypothalamus-pituitary-adrenal-axis activity...
<h3>Abstract</h3> The marble burying test is a commonly used paradigm to describe phenotypes in mouse models of neurodevelopmental and psychiatric disorders. current methodological approach relies predominantly on reporting the number buried marbles at end test. By measuring proxy behavior (buried marbles), many important characteristics regarding temporal aspect this assay are lost. Here, we introduce novel, automated method quantify during with focus bouts movement dynamics. Using...
Clinical evidence suggests that developmental cerebellar injury and cerebello-cortical connectivity abnormalities are often present in autism. In mouse models, cerebellar-specific deletions of autism risk genes, or temporally constrained, manipulations circuits, elicit autistic-like behaviors. Nonetheless, behavioral electrophysiological findings inconsistent within across models. Additionally, while during development can induce autistic phenotypes, studies early function scarce. this...
The phosphoinositide-3-kinase (PI3K) family plays a major role in cell signaling and is predominant leukocytes. Gain-of-function (GOF) mutations the PIK3CD gene lead to development of activated PI3Kδ syndrome (APDS), rare primary immunodeficiency disorder. A subset APDS patients also displays neurodevelopmental delay symptoms, suggesting potential cognitive behavioural function. However, extent nature deficits has not been previously quantified. Here, we assessed functions two patients,...
Abstract Background The balance beam assay is a well-known paradigm to assess motor coordination in mouse models of neurodegenerative diseases. Classically, these experiments have been quantified using manual annotation, which time-consuming and prone inter-experimenter variability. Methods We present an open-source analysis pipeline that allows for the automated quantification function. Using established ataxia model, we validated by comparing its output three independent observers. Results...
The glucocorticoid stress hormones affect brain function via high-affinity mineralocorticoid receptors (MRs) and lower-affinity (GRs). MR GR not only differ in affinity for ligands, but also have distinct, sometimes opposite, actions on neuronal excitability other cellular higher-order parameters related to cerebral function. messenger RNA (mRNA) levels are often used as a proxy the responsiveness glucocorticoids, assuming proportionality between mRNA protein levels. This may be especially...
Abstract Current phenotyping approaches for murine autism models often focus on one selected behavioral feature, making the translation onto a spectrum of autistic characteristics in humans challenging. Furthermore, sex and environmental factors are rarely considered. Here, we aimed to capture full manifestations three mouse develop “behavioral fingerprint” that takes influences under consideration. To this end, employed wide range classical standardized tests; two multi-parametric assays:...
Current phenotyping approaches for murine autism models often focus on one selected behavioral feature, making the translation onto a spectrum of autistic characteristics in humans challenging. Furthermore, sex and environmental factors are rarely considered. Here, we aimed to capture full manifestations three mouse develop "behavioral fingerprint" that takes influences under consideration. To this end, employed wide range classical standardized tests; two multi-parametric assays: Live Mouse...
Abstract The phosphoinositide-3-kinase (PI3K) family plays a major role in cell signalling and is predominant leukocytes. Gain-of-function (GOF) mutations the PIK3CD gene lead to development of activated PI3Kδ syndrome (APDS), rare primary immunodeficiency disorder. A subset APDS patients also displays neurodevelopmental delay symptoms, suggesting potential cognitive behavioural function. However, extent nature deficits has not been previously quantified. Here, we assessed functions two...
Abstract The marble burying test is a commonly used paradigm to screen phenotypes in mouse models of neurodevelopmental and psychiatric disorders. current methodological approach relies solely on reporting the number buried marbles at end test. By measuring proxy behavior (buried marbles), rather than itself (burying bouts), many important characteristics regarding temporal aspect this assay are lost. Here we introduce novel, automated method quantify throughout duration with focus bouts....