Environmental novelty potently prevents impairment of   hippocampal synaptic plasticity by Aβ oligomers        via a β2-ad...
Expose young mice for 4 weeks (2-6 wk old) to a complex environment ofnovel objects they can explore from 9:00 – 5:00. Cha...
Golgi staining of hippocampus: dendritic spine area, length   and volume -- but not density – are increased by exposure to...
EE exposure enhances hippocampal LTP
EE training prevents LTP inhibition by synthetic Aß S26C dimers, and importantly, by Aß dimers isolated directly from AD c...
Exposure to EE enhances levels of ß2-AR but notß1-AR, DR1, DR2 and other monoamine receptors
EE rescue of Aβ-impaired LTP is β-adrenergic dependent
Soluble Aß oligomers induce a time-dependent decrease in ß2-AR levelsin hippocampal membranes -- selectively among monoami...
Prolonged oral administration of a b-adrenergicantagonist prevents EE from rescuing the Aß inhibition of LTP
Prolonged oral administration of the b-adrenergic agonist isoproternol to SH mice mimics the benefit of EE on LTP
Two months of EE in mid-adulthood producessimilar benefit as one month of EE in juvenile mice
Novelty vs. exercise in enhancing hippocampal LTP
Prolonged exposure to novelty contributes more to prevention    of Aβ-impaired LTP than does prolonged exercise alone
Use It or Lose It?Exposing healthy, wild-type mice to a novel environment producesseveral benefits for hippocampal structu...
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Li et al neuron webinar 3-20-13

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Presentation made by Dr. Dennis Selkoe at the Alzheimer Research Forum Live Webinar of March 20, 2013 - http://www.alzforum.org/res/for/journal/detail.asp?liveID=209

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Li et al neuron webinar 3-20-13

  1. 1. Environmental novelty potently prevents impairment of hippocampal synaptic plasticity by Aβ oligomers via a β2-adrenergic signaling pathway Shaomin Li*, Ming Jin*, Dainan Yang, Ting Yang, Thomas Koeglsperger, Hongjun Fu and Dennis Selkoe Center for Neurologic Diseases Brigham and Women’s Hospital Harvard Medical School Neuron - March 6, 2013
  2. 2. Expose young mice for 4 weeks (2-6 wk old) to a complex environment ofnovel objects they can explore from 9:00 – 5:00. Change the “toys” each day.
  3. 3. Golgi staining of hippocampus: dendritic spine area, length and volume -- but not density – are increased by exposure to EEStandard housing Enriched environment
  4. 4. EE exposure enhances hippocampal LTP
  5. 5. EE training prevents LTP inhibition by synthetic Aß S26C dimers, and importantly, by Aß dimers isolated directly from AD cortex
  6. 6. Exposure to EE enhances levels of ß2-AR but notß1-AR, DR1, DR2 and other monoamine receptors
  7. 7. EE rescue of Aβ-impaired LTP is β-adrenergic dependent
  8. 8. Soluble Aß oligomers induce a time-dependent decrease in ß2-AR levelsin hippocampal membranes -- selectively among monoamine receptors Membrane b2AR b1AR DR1 DR2 TR
  9. 9. Prolonged oral administration of a b-adrenergicantagonist prevents EE from rescuing the Aß inhibition of LTP
  10. 10. Prolonged oral administration of the b-adrenergic agonist isoproternol to SH mice mimics the benefit of EE on LTP
  11. 11. Two months of EE in mid-adulthood producessimilar benefit as one month of EE in juvenile mice
  12. 12. Novelty vs. exercise in enhancing hippocampal LTP
  13. 13. Prolonged exposure to novelty contributes more to prevention of Aβ-impaired LTP than does prolonged exercise alone
  14. 14. Use It or Lose It?Exposing healthy, wild-type mice to a novel environment producesseveral benefits for hippocampal structure and functionThese benefits make the EE mice substantially resistant to the acutesynaptic toxicity of soluble Ab oligomers isolated from AD cortexAmong numerous signaling cascades augmented by EE, a b 2-adrenergicpathway shows more enhancement than other monoamine receptorsAccordingly, we can mimic the EE resistance to Aß oligomers byprolonged feeding of a b-adrenergic agonist (isoproterenol) to SH miceProlonged exposure to a novel environment promotes resistance to Ab oligomers more effectively than does prolonged exerciseThe benefits of EE exposure can be observed not just in juvenile mice but also in middle-aged mice if done longer

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