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SYRCLE_Reus mini symposium sr animal studies 30082012
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SYRCLE_Reus mini symposium sr animal studies 30082012


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  • 1. Pediatric Physical TherapyAfd. Kinderfysiotherapie
  • 2. Can animal models provide insight into neuromuscular functioning in Prader Wili syndrome?Dr. Carlijn HooijmansDr. Janielle van Alfen-van der VeldenProf. dr. Merel Ritskes-HoitingaProf. dr. Ria Nijhuis-van der SandenLinda Reus, MSc. Afd. Kinderfysiotherapie
  • 3. In this talk • Prader Willi syndrome and motor performance • PWS animal models • Systematic literature search • Results • Discussion Afd. Kinderfysiotherapie
  • 4. The classical PWS patient Small Hyperphagia Obesety Chromosome 15 Afd. Kinderfysiotherapie
  • 5. The most prominent characteristics of PWS • Infant hypotonia • Abnormal body composition: Fat mass ↑ Muscle mass ↓ • Metabolism ↓ • Muscle strength ↓ • Hypogonadism • Obesity • Short stature • Motor problems • Cognitive and behavioral defects • Mild dysphormic facial features Afd. Kinderfysiotherapie
  • 6. Motor problems in PWS infants • Hypotonia, • Failure to thrive • Feeding problems • Fat mass↑, Muscle mass ↓ Muscle force↓ • Inactivity • Comprehension of motor skills↓ Independent sitting: 11-13 months Independent walking: 30-34 months First spoken words: 21-23 months Afd. Kinderfysiotherapie
  • 7. Typical motor development(9-months-old) Afd. Kinderfysiotherapie
  • 8. Motor functioning in PWS infant(9-months-old) Afd. Kinderfysiotherapie
  • 9. Systematic review on motor problems in PWS(no animal studies included) A lot of reports Reports are scarce Infancy Children and Adults Motor Muscle Motor development is performance↓ strength↓ seriously delayed Physical Activity↓ fitness↓ Afd. Kinderfysiotherapie
  • 10. Systematic review on causes of motor problems in PWS(no animal studies included) Only pilot studies 70% decreased A lot of evidence muscle strength 25-37% decreased Muscle mass Abnormal muscle tissue Neurological abnormalities Afd. Kinderfysiotherapie
  • 11. Conclusions and questions • Body composition: fat mass↑, muscle mass↓ Does not solely explain motor problems in PWS • Can animal models provide more insight into neuromuscular functioning in PWS? • Is there an animal model suited to study effects of training or medication on the neuromuscular system? Afd. Kinderfysiotherapie 10
  • 12. PWS animal models • Full genetic mouse models (PWS-IC, TgPWS) • Micro deletion or knock-out mouse models (a.o. Magel2, Necdin) Afd. Kinderfysiotherapie 11
  • 13. SR animal models: literature search Afd. Kinderfysiotherapie 12
  • 14. Neurological development: 6 articles Necdin knock-out mouse models •Necdin is one of the 5 genes related to PWS •Necdin was the first gene studied in PWS models •Its neuro-developmental function is extensively studied • Cell growth • Cell migration • Cell differentiation • Cell death/survival Afd. Kinderfysiotherapie 13
  • 15. Neuromuscular functioning: 2 articlesBehavior Necdin knock-out mouse models • Breathing disorders • Behavioral abnormalities • Sensory defects • Abnormal hypothalamic nuclei Adult mice • Normal: weight, activity, exploration, muscle strength • Abnormal: slip↑, balance↓, running↓ Infant mice (10-days-old) • Abnormal motor activity, muscle strength↓ Afd. Kinderfysiotherapie 14
  • 16. Neuromuscular functioning: 2 articles31% motoneuron cell death Afd. Kinderfysiotherapie 15
  • 17. Neuromuscular functioning: 2 articles31% cell death motoneurons During embryonic development •Increased natural occurring cell death motoneurons •31% loss of lumbar motoneurons 11-day-old mouse • 27% loss of lumbar motoneurons Conclusion: •The lack of Necdin is involved in motor deficiency in PWS patients Afd. Kinderfysiotherapie 16
  • 18. Motor activity: 1 article Magel2-null mouse model • Decreased growth • Excessive weight gain • Increased fat mass • Abnormal metabolism • Decreased motor activity Conclusion •Inactivity presumably caused by depression Afd. Kinderfysiotherapie 17
  • 19. Conclusion Not suited • Full genetic mouse models • Magel2-null mouse model Possibly suited • Necdin knock-out mouse model Afd. Kinderfysiotherapie 18
  • 20. Questions?Afd. Kinderfysiotherapie 19