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Presented by: Justin P. Smith

Brain-derived neurotrophic factor plasma levels in patients suffering from post-traumatic stress disorder. Liliana Dell'Osso a, Claudia Carmassi a,⁎, Alessandro Del Debbio a, Mario Catena Dell'Osso a, Carolina Bianchi a,

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Presented by: Justin P. Smith

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  1. Brain-derived neurotrophic factor plasma levels in patients suffering frompost-traumatic stress disorder Liliana Dell'Osso a, Claudia Carmassi a,⁎, Alessandro Del Debbio a, Mario Catena Dell'Osso a, Carolina Bianchi a, Eleonora da Pozzo a, Nicola Origlia b, Luciano Domenici b,c, Gabriele Massimetti a, Donatella Marazziti a, Armando Piccinni a Presented by: Justin P. Smith

  2. PTSD Exposure • Combat or military exposure • Child sexual or physical abuse • Terrorist attacks • Sexual or physical assault • Serious accidents, such as a car wreck. • Natural disasters, such as a fire, tornado, hurricane, flood, or earthquake

  3. How PTSD Develops • How intense the trauma was or how long it lasted • If you lost someone you were close to or were hurt • How close you were to the event • How strong your reaction was • How much you felt in control of events • How much help and support you got after the event

  4. Common Symptoms • Reliving the event (also called re-experiencing symptoms)- memory recall • Avoiding situations that remind you of the event- avoiding stimulation, context • Feeling numb- blunted affect • Feeling keyed up (also called hyperarousal)- over active amygdala?

  5. BDNF- Brain Derived Neurotrophic Factor • Protein, from BDNF-gene • Promotes cell survival & regulates proliferation and differentiation of neurons • Stress down regulates BDNF mRNA • Upregulated during learning • Necessary for LTP

  6. BDNF cont • Role in: growth, development, maintenance and function of neuronal systems • Modulates synaptic plasticity and neurotransmitter release & intracellular signal-transduction

  7. BDNF & TrkB • TrkB- protein-tyrosine kinase receptor • Together help with LTP (long lasting synaptic plasticity) • Role in learning and memory • Role in pathogenesis of mood and anxiety disorders

  8. BDNF and TrkB • TrkB- intracellular kinase-activating receptor

  9. BDNF & TrkB in Rats after PSS • Predator Scent Stress – place rat on soiled litter for 10 min. (controls on unsoiled litter) • 7 Days later....... • Found in CA1 (of hippocampus): • Down-regulated BDNF mRNA • Upregulated TrkB • Fits-less BDNF - need more receptors!

  10. Western Blot- Protein RT-PCR

  11. Hippocampus

  12. Rat Hippocampus

  13. CA1

  14. Role of Hippocampus • Long term memory and spatial navigation

  15. THIS IS STRESSFUL!

  16. Predisposed to Stress • Rats given corticosterone in drinking water had a decrease in NMDA (NR2B), AMPA subunits, GluR2/3 & BDNF • Also looked at fear extinction learning: ok to be in this place now….

  17. Receptors NMDA-Ionotropic

  18. Figure 112"> Benarroch, E. E. Neurology 2008;70:964-968

  19. Oral Corticosterone cont.

  20. Oral Corticosterone

  21. Take Away • Predisposed stress can decrease fear extinction… • Make it harder to learn that “its” O-K.

  22. 1st study looking at BDNF w/ PTSD • PTSD patients would be expected to have lower BDNF levels • Hippocampus, Amygdala and Cingulate (limbic system) involved • fMRI of PTSD show decreased hippocampal volume • + correlation blood-brain BDNF levels

  23. Methods • 18 PTSD, 18 Controls • How long did PTSDers have PTSD? • Blood collected 8-9am (following fast) • ELISA

  24. 22% (8%)

  25. PTSD vs. Control

  26. # of traumas

  27. +/- 1 year from trauma

  28. Discussion • BDNF lower in PTSD • Limits • Small sample size • BDNF in blood not brain • Possible role of BDNF in PTSD • Predator vs. Prey attitude among individuals exposed to the same stress

  29. Thank You

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