scholarly journals Heterozygous CDKL5 Knockout Female Mice Are a Valuable Animal Model for CDKL5 Disorder

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Claudia Fuchs ◽  
Laura Gennaccaro ◽  
Stefania Trazzi ◽  
Stefano Bastianini ◽  
Simone Bettini ◽  
...  
Keyword(s):  
Animal Model ◽  
Hippocampal Neurons ◽  
Motor Coordination ◽  
Neurodevelopmental Disorder ◽  
Preclinical Studies ◽  
Spine Density ◽  
Heterozygous Female ◽  
Comprehensive Overview ◽  
Age Related ◽  
Cdkl5 Disorder

CDKL5 disorder is a severe neurodevelopmental disorder caused by mutations in the X-linked CDKL5 (cyclin-dependent kinase-like five) gene. CDKL5 disorder primarily affects girls and is characterized by early-onset epileptic seizures, gross motor impairment, intellectual disability, and autistic features. Although all CDKL5 female patients are heterozygous, the most valid disease-related model, the heterozygous female Cdkl5 knockout (Cdkl5 +/−) mouse, has been little characterized. The lack of detailed behavioral profiling of this model remains a crucial gap that must be addressed in order to advance preclinical studies. Here, we provide a behavioral and molecular characterization of heterozygous Cdkl5 +/− mice. We found that Cdkl5 +/− mice reliably recapitulate several aspects of CDKL5 disorder, including autistic-like behaviors, defects in motor coordination and memory performance, and breathing abnormalities. These defects are associated with neuroanatomical alterations, such as reduced dendritic arborization and spine density of hippocampal neurons. Interestingly, Cdkl5 +/− mice show age-related alterations in protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signaling, two crucial signaling pathways involved in many neurodevelopmental processes. In conclusion, our study provides a comprehensive overview of neurobehavioral phenotypes of heterozygous female Cdkl5 +/− mice and demonstrates that the heterozygous female might be a valuable animal model in preclinical studies on CDKL5 disorder.

scholarly journals SHR/NCrl rats as a model of ADHD can be discriminated from controls based on their brain, blood, or urine metabolomes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Camille Dupuy ◽  
Pierre Castelnau ◽  
Sylvie Mavel ◽  
Antoine Lefevre ◽  
Lydie Nadal-Desbarats ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Attention Deficit Hyperactivity Disorder ◽  
Animal Model ◽  
Metabolic Pathways ◽  
Neurodevelopmental Disorder ◽  
Hyperactivity Disorder ◽  
Pathophysiological Condition ◽  
The Brain ◽  
And Oxidative Stress ◽  
Peripheral Samples

AbstractAttention-Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorder characterized by inattention, impulsivity, and hyperactivity. The neurobiological mechanisms underlying ADHD are still poorly understood, and its diagnosis remains difficult due to its heterogeneity. Metabolomics is a recent strategy for the holistic exploration of metabolism and is well suited for investigating the pathophysiology of diseases and finding molecular biomarkers. A few clinical metabolomic studies have been performed on peripheral samples from ADHD patients but are limited by their access to the brain. Here, we investigated the brain, blood, and urine metabolomes of SHR/NCrl vs WKY/NHsd rats to better understand the neurobiology and to find potential peripheral biomarkers underlying the ADHD-like phenotype of this animal model. We showed that SHR/NCrl rats can be differentiated from controls based on their brain, blood, and urine metabolomes. In the brain, SHR/NCrl rats displayed modifications in metabolic pathways related to energy metabolism and oxidative stress further supporting their importance in the pathophysiology of ADHD bringing news arguments in favor of the Neuroenergetic theory of ADHD. Besides, the peripheral metabolome of SHR/NCrl rats also shared more than half of these differences further supporting the importance of looking at multiple matrices to characterize a pathophysiological condition of an individual. This also stresses out the importance of investigating the peripheral energy and oxidative stress metabolic pathways in the search of biomarkers of ADHD.

scholarly journals Age-Related Changes in the Primary Motor Cortex of Newborn to Adult Domestic Pig Sus scrofa domesticus

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2019
Author(s):  
Salvatore Desantis ◽  
Serena Minervini ◽  
Lorenzo Zallocco ◽  
Bruno Cozzi ◽  
Andrea Pirone
Keyword(s):  
Animal Model ◽  
Motor Cortex ◽  
Calcium Binding ◽  
Sus Scrofa ◽  
Primary Motor Cortex ◽  
Morphological Changes ◽  
Neural Cells ◽  
Age Related ◽  
Cell Layers ◽  
Sus Scrofa Domesticus

The pig has been increasingly used as a suitable animal model in translational neuroscience. However, several features of the fast-growing, immediately motor-competent cerebral cortex of this species have been adequately described. This study analyzes the cytoarchitecture of the primary motor cortex (M1) of newborn, young and adult pigs (Sus scrofa domesticus). Moreover, we investigated the distribution of the neural cells expressing the calcium-binding proteins (CaBPs) (calretinin, CR; parvalbumin, PV) throughout M1. The primary motor cortex of newborn piglets was characterized by a dense neuronal arrangement that made the discrimination of the cell layers difficult, except for layer one. The absence of a clearly recognizable layer four, typical of the agranular cortex, was noted in young and adult pigs. The morphometric and immunohistochemical analyses revealed age-associated changes characterized by (1) thickness increase and neuronal density (number of cells/mm2 of M1) reduction during the first year of life; (2) morphological changes of CR-immunoreactive neurons in the first months of life; (3) higher density of CR- and PV-immunopositive neurons in newborns when compared to young and adult pigs. Since most of the present findings match with those of the human M1, this study strengthens the growing evidence that the brain of the pig can be used as a potentially valuable translational animal model during growth and development.

Developmental coordination disorder is more than a motor problem: Children describe the impact of daily struggles on their quality of life

2017 ◽  
Vol 81 (2) ◽  
pp. 65-73 ◽  
Author(s):  
Jill G Zwicker ◽  
Melinda Suto ◽  
Susan R Harris ◽  
Nikol Vlasakova ◽  
Cheryl Missiuna
Keyword(s):  
Quality Of Life ◽  
Motor Coordination ◽  
Developmental Coordination Disorder ◽  
Neurodevelopmental Disorder ◽  
Emotional Impact ◽  
Qualitative Researcher ◽  
Motor Problem ◽  
Coordination Disorder ◽  
The Impact

Introduction Affecting 5–6% of children, developmental coordination disorder is a neurodevelopmental disorder characterized by poor motor coordination and difficulty learning motor skills. Although quantitative studies have suggested that children with developmental coordination disorder experience reduced quality of life, no known qualitative studies have reported what daily life is like from their perspective. Method Guided by an inductive realistic approach and using semi-structured, individual interviews, 13 children (8–12 years) were asked to describe what life is like in their own words. Three researchers coded interviews manually to identify relevant content. An experienced qualitative researcher conducted a second, in-depth thematic analysis using NVivo to identify patterns and themes. Findings Two themes – milestones as millstones and the perils of printing – illuminated participants’ challenges in completing everyday activities at home and at school. The third theme – more than a motor problem – revealed the social and emotional impact of these struggles and from being excluded from play. The fourth theme – coping strategies – described their efforts to be resilient. Conclusion Parents, educators, physicians, and therapists working with children with developmental coordination disorder must recognize how their quality of life is affected by the physical and emotional toll of their efforts to participate successfully in daily activities.

scholarly journals Differences in the Motor Coordination Abilities Among Adolescent Gymnasts, Swimmers, and Ice Hockey Players

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Timo Jaakkola ◽  
Anthony Watt ◽  
Sami Kalaja
Keyword(s):  
Motor Coordination ◽  
Ice Hockey ◽  
Specific Training ◽  
Young Athletes ◽  
Test Protocol ◽  
Male Adolescents ◽  
Age Related ◽  
Study Results ◽  
Hockey Players ◽  
Better Than

AbstractPurpose. Motor coordination is proposed to be a relatively stable age-related construct, unlikely to be influenced by aligned experiential factors such as intensive sport-specific training. The purpose of the study is to investigate if there are differences in motor coordination abilities among young artistic gymnasts, swimmers, and ice hockey players.Methods. The participants of the study were 508 female and 258 male adolescents (age, M = 12.80, SD = 1.10) comprising artistic gymnasts (n = 463), swimmers (n = 70), and ice hockey players (n = 233). The KTK-test protocol was used to analyse their gross motor coordination abilities.Results. The results of the study demonstrated that gymnasts scored better than ice hockey players and swimmers in the test of walking backwards along a beam, and better than ice hockey players in total motor coordination, hopping over an obstacle, and the test of moving sideways on wooden boards. However, ice hockey players scored higher than swimmers and gymnasts in the test of jumping from side to side. Subsequently, swimmers obtained better results in the test of moving sideways on wooden boards as compared with ice hockey players.Conclusions. The study results indicate that intensive sport-specific training may extend young athletes′ motor coordination characteristics in the ability areas representative of the sport in which they engage.

scholarly journals Effects of Cyclophosphamide and/or Doxorubicin in a Murine Model of Postchemotherapy Cognitive Impairment

2017 ◽  
Vol 162 (2) ◽  
pp. 462-474 ◽  
Author(s):  
Timothy J Flanigan ◽  
Julie E Anderson ◽  
Ikram Elayan ◽  
Antiño R Allen ◽  
Sherry A Ferguson
Keyword(s):  
Cognitive Impairment ◽  
Dentate Gyrus ◽  
Test Performance ◽  
Motor Coordination ◽  
Human Condition ◽  
Spatial Learning And Memory ◽  
Exact Nature ◽  
Spine Density ◽  
Breast Cancer Patients ◽  
Route Of Exposure

Abstract Postchemotherapy cognitive impairment, or PCCI, is a common complaint, particularly among breast cancer patients. However, the exact nature of PCCI appears complex. To model the human condition, ovariectomized C57BL/6J mice were treated intravenous weekly for 4 weeks with saline, 2 mg/kg doxorubicin (DOX), 50 mg/kg cyclophosphamide (CYP), or DOX + CYP. For the subsequent 10 weeks, mice were assessed on several behavioral tests, including those measuring spatial learning and memory. After sacrifice, hippocampal spine density and morphology in the dentate gyrus, CA1, and CA3 regions were measured. Additionally, hippocampal levels of total glutathione, glutathione disulfide, MnSOD, CuZnSOD, and cytokines were measured. Body weight decreased in all groups during treatment, but recovered post-treatment. Most behaviors were unaffected by drug treatment: Open field activity, motor coordination, grip strength, water maze and Barnes maze performance, buried food test performance, and novel object and object location recognition tests. There were some significant effects of CYP and DOX + CYP treatment during the initial test of home cage behavior, but these did not persist into the second and third test times. Density of stubby spines, but not mushroom or thin spines, in the dentate gyrus was significantly decreased in the DOX, CYP, and DOX + CYP treatment groups. There were no significant effects in the CA1 or CA3 regions. CuZnSOD levels were significantly increased in DOX + CYP-treated mice; other hippocampal antioxidant levels were unaffected. Most cytokines showed no treatment-related effects, but IL-1β, IL-6, and IL-12 were slightly reduced in mice treated with DOX + CYP. Although the animal model, route of exposure, and DOX and CYP doses used here were reflective of human exposure, there were only sporadic effects due to chemotherapeutic treatment.

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