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 Presented by: Justin P. Smith
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
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
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
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
BDNF cont Role in: growth, development, maintenance and function of neuronal systems Modulates synaptic plasticity and neurotransmitter release & intracellular signal-transduction
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
BDNF and TrkB TrkB- intracellular kinase-activating receptor
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!
Western Blot- Protein RT-PCR
Hippocampus
Rat Hippocampus
CA1
Role of Hippocampus Long term memory and spatial navigation
THIS IS STRESSFUL!
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….
Receptors NMDA-Ionotropic
Benarroch, E. E. Neurology 2008;70: Figure 112">
Oral Corticosterone cont.
Oral Corticosterone
Take Away Predisposed stress can decrease fear extinction… Make it harder to learn that “its” O-K.
1 st 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
Methods 18 PTSD, 18 Controls How long did PTSDers have PTSD? Blood collected 8-9am (following fast) ELISA
22% (8%)
PTSD vs. Control
# of traumas
+/- 1 year from trauma
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
Thank You