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Brain-derived neurotrophic factor plasma levels in patients suffering from post-traumatic stress disorder

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Brain-derived neurotrophic factor plasma levels in patients suffering from post-traumatic stress disorder

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    2. 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, Eleonora da Pozzo a, Nicola Origlia b, Luciano Domenici b,c, Gabriele Massimetti a, Donatella Marazziti a, Armando Piccinni a

    3. 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

    4. 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

    5. 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? Common Symptoms

    6. 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

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

    8. 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

    9. BDNF and TrkB TrkB- intracellular kinase-activating receptor Signaling pathways of BDNF/TrkB activation in learning and memory. Activity increases BDNF expression and release from pre- and postsynaptic sites. BDNF binds to TrkB receptors located on presynaptic axons, leading to its auto-phosphorylation and activation of the signal transduction MAPK pathway, facilitating neurotransmitter release. BDNF also binds to postsynaptic TrkB, leading to the activation of AMPA and NMDA receptors through the activation of the MAPK and PLC pathways that lead the subsequent phosphorylation of PKA, CAMK, and CREB. Signaling pathways of BDNF/TrkB activation in learning and memory. Activity increases BDNF expression and release from pre- and postsynaptic sites. BDNF binds to TrkB receptors located on presynaptic axons, leading to its auto-phosphorylation and activation of the signal transduction MAPK pathway, facilitating neurotransmitter release. BDNF also binds to postsynaptic TrkB, leading to the activation of AMPA and NMDA receptors through the activation of the MAPK and PLC pathways that lead the subsequent phosphorylation of PKA, CAMK, and CREB.

    10. 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!

    15. CA1

    16. Role of Hippocampus Long term memory and spatial navigation The mossy fibres are the axons of DG granule cells. They extend from the dendate gyrus to CA3 pyramidal cells, forming their major input. MF synapses on CA neurons are large aggregations of termini, with multiple transmitter release sites and post-synaptic densities. Multiple granule cells can synapse onto a single CA3 pyramidal cell.The mossy fibres are the axons of DG granule cells. They extend from the dendate gyrus to CA3 pyramidal cells, forming their major input. MF synapses on CA neurons are large aggregations of termini, with multiple transmitter release sites and post-synaptic densities. Multiple granule cells can synapse onto a single CA3 pyramidal cell.

    18. 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.

    19. Receptors NMDA-Ionotropic

    21. Oral Corticosterone cont.

    22. Oral Corticosterone

    23. Take Away Predisposed stress can decrease fear extinction Make it harder to learn that its O-K.

    25. 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

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

    28. PTSD vs. Control

    31. 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

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