SYRCLE_Reus mini symposium sr animal studies 30082012

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SYRCLE_Reus mini symposium sr animal studies 30082012

  1. 1. Pediatric Physical TherapyAfd. Kinderfysiotherapie
  2. 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. 3. In this talk • Prader Willi syndrome and motor performance • PWS animal models • Systematic literature search • Results • Discussion Afd. Kinderfysiotherapie
  4. 4. The classical PWS patient Small Hyperphagia Obesety Chromosome 15 Afd. Kinderfysiotherapie
  5. 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. 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. 7. Typical motor development(9-months-old) Afd. Kinderfysiotherapie
  8. 8. Motor functioning in PWS infant(9-months-old) Afd. Kinderfysiotherapie
  9. 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. 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. 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. 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. 13. SR animal models: literature search Afd. Kinderfysiotherapie 12
  14. 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. 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. 16. Neuromuscular functioning: 2 articles31% motoneuron cell death Afd. Kinderfysiotherapie 15
  17. 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. 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. 19. Conclusion Not suited • Full genetic mouse models • Magel2-null mouse model Possibly suited • Necdin knock-out mouse model Afd. Kinderfysiotherapie 18
  20. 20. Questions?Afd. Kinderfysiotherapie 19

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