1) This study aimed to screen for differences in mitochondrial protein expression in mouse models of anxiety (Black 6 and Dilute Brown Non-Agouti mice) and examine the effects of ketamine treatment on immune marker levels in wild type mice. 2) The screening found higher expression of the glutamine synthetase protein (GLUL) in Black 6 mice compared to Dilute Brown Non-Agouti mice. 3) Ketamine treatment did not produce differences in the levels of immune markers (IL-1β, IL-6, and TNFα) between treated and untreated wild type mice.

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Quantitative protein estimation in anxiety
and mood disorder mouse models
Igor Stošić, Giuseppina Maccarrone, Christiane Rewerts, Christoph Turck.
RG Proteomics and Biomarkers, Dep. Translational Research in Psychiatry,
Max Planck Institute for Psychiatry
Methods
Max Planck Institute
of Psychiatry
German Research Institute of Psychiatry
Results5
1 Introduction and Aim of study
2 Results
Anxiety and mood disorders have high incidence in the
population and are linked to numerous issues in therapy like
delayed onset and high therapy resistance. Furthermore, there
is no standardized diagnostic test for these disorders, the
diagnosis relies on subjective description of the symptoms from
the patients.
Anxiety and depression disorders are becoming a big burden in
the modern society, resulting in enormous personal suffering
and economic loss and being major risk factors.1
Recent proteomic studies on anxiety disorder showed an increment
of mitochondrial proteins expression and activity.2 The aim of this
study was to screen mitochondrial proteins in DBA and B6 anxiety
mouse model to determine new expression protein differences.
Depression disorder is linked with neuronal atrophy and
inflammation.3 New possibility of treatment is glutamatergic
modulation (excitation) with ketamine. We studied the effect of
ketamine on immune markers expression: IL-1β, IL-6 and TNFα in
treated wild type mice.
Black 6 (B6) anxious
Dilute Brown
Non-Agouti
(DBA)
anxious
protein
estimation-
Bradford assay
protein
extract
1D-SDS gel
electrophoresis
protein
transfer
immunodetectionimagingdata
analysis
ELISA
4
ketamine
treated
vehicle
treated
plasma
samples
anti cytokine Ab
coated micro-titer
plate
protein binding
to Ab
labeled Absubstratemeasurements
6
CD1
hippocampi
cell lysates
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0.02
0 10 20
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0.01
0.02
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Western blot
Samples
Selectively inbred
high anxiety
behaviour (HAB) CD1
MitoQ
treated
vehicle
treated
mice brain
harvest
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Methods
plasma
samples
hippocampi
cell lysates
TNFα conc. (pg/ml)
(plasma)
IL-6 conc. (pg/ml)
(plasma)
IL-1β conc. (pg/ml)
cell lysates
HAB - CD1 MnSOD ([Mn] Superoxide dismutase) SOD1 ([Cu-Zn] Superoxide dismutase)
B6 vs. DBA
Tim23
GPX3 (Glutathione peroxidase 3) GLUL (Glutamine synthetase)
standards vehicle treated (CT)ketamine treated (K)
responders non responders
Conclusions
• Responders to MitoQ treatment have trend for high expression of SOD1 cytoplasmic isoform
• The screening of mitochondrial and cytoplasmic proteins in B6 and DBA mice showed high expression of glutamine synthetase (GLUL)
in B6.
• No immune marker level differences in ketamine treated and untreated mice were found.
statistical analysis: Mann Whitney U test
IDH (Isocitrate dehydrogenase)
R – responders
NR- non responders
3
Samples
MnSOD ([Mn] Superoxide dismutase) SOD1 ([Cu-Zn] Superoxide dismutase)
(Mitochondrial import inner
membrane translocase subunit)
1 Diagnostic Issues in Depression and Generalized Anxiety Disorder, American Psychiatric Association (APA)
2 Proteomics and Metabolomics Analysis of a Trait Anxiety Mouse Model Reveals Divergent Mitochondrial Pathways, Filiou M. and al.
3 Neuroplasticity and the next wave of antidepressant strategies, Hayley S. and Litteljohn D.
References:
Acknowledgements
No statistically significant
differences were observed
norm.values
I thank Katja Weckmann and Dr. Michaela Filiou for help and providing mice plasma and brain samples.
I thank Amgen Foundation for the financial support.