presented by: justin p. smith
DESCRIPTION
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, - PowerPoint PPT PresentationTRANSCRIPT
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;70:964-968
Figure 112">
Oral Corticosterone cont.
Oral Corticosterone
Take Away
• Predisposed stress can decrease fear extinction…
• Make it harder to learn that “its” O-K.
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
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