1. No category

Effect of Deep Brain
Stimulation on Microglia
Pelle de Koning, M.D.
Amsterdam Medical Center
Bidirectional Microglia-Neuron Communication
1.
2.
Eyo & Wu, Neural Plast, 2013
Microglia reduce Neuronal Activity
Li et al., Dev Cell, 2012
Microglia also affect long-term
neuronal activity
1. Altering number of functional synapses
2. Inducing Neurogenesis
3. Altering synaptic plasticity of Neurons
Microglia affect behaviour
Chen et al, Cell 2010
Obsessive-compulsive disorder
obsessions: repetitive ideas or images
compulsions: repetitive ritualistic acts
OCD:
Hyperactive networks
ACC
OFC
PUT
CAU
OFC: orbitofrontal cortex
ACC: anterior cingulate cortex
CAU: caudate
PUT: putamen
AMYG: amygdala
Deep Brain Stimulation (DBS) for
Obsessive-Compulsive Disorder
DBS-OCD=46
DBS for OCD
responder: 56%
Figee et al., Nat Neurosci 2013
De Koning et al., Curr Psych Rep 2012
Does DBS alter microglia function?
Is OCD associated
with microglia activation?
Cytokines
Imaging (PET)
Post-Mortem
Animal
Cytokines
Imaging (PET)
Post-Mortem
Animal
Cytokines
DBS
OFF
DBS ON
VS
N=16
DBS ON
40
32
DBS ON
DBS OFF
DBS OFF
275
*
*
220
*
24
165
16
110
8
55
0
0
Y-BOCS
HAM-A
HAM-D
*
Cortisol
Noradrenalin
De Koning et al, Psychoneuroendocrinology, 2013
Cytokines
DBS ON
VS DBS OFF
N=16
*
CRP
IFNγ
IL-8
CCL2/MCP-1
CXCL1/GROa
CXCL10/IP-10
*
CCL4/MIP-1b
Cytokines
Imaging (PET)
Post-Mortem
Animal
Post-Mortem
•
•
•
•
NAc DBS
Euthanasia
Higher Voltages
Electrode / Tract surrounding tissues
Post-operative CT
Post-mortem MRI
Post-Mortem
Post-Mortem
Post-Mortem
Brown =
activated microglia
(HLA-DR staining)
A/B/C = Microglia surrounding Tract
E/F = Many Microglia in
Internal Capsule
Post-Mortem
•
•
•
Gliosis in tissue surrounding the tract
Mild Microglia activation around tract
Many activated microglia in IC
Cytokines
Imaging (PET)
Post-Mortem
Animal
Animal
SAPAP3-KO
Goal:
1. Microglia alterations in SAPAP3 mice?? (similar to HOXB8??)
2. Does DBS alter microglia in SAPAP3 mice
Animal
Frontal Cortex
Striatum
Internal Capsule
Amygdala
Preliminary Data
4 SAPAP3 & 4 Control (C57BI6)
Cytokines
Imaging (PET)
Post-Mortem
Animal
Cytokines
DBS increases cytokines
Post-Mortem
Microglia around electrode
Animal
Less microglia in striatum / PFC
Imaging (PET)
?
Future Directions
•
SAPAP3 DBS
•
Netherlands Brain Bank OCD/Microglia
•
Measure cytokines in CSF
•
PET in OCD patients / DBS
[email protected]
[email protected]