Selectively inbred animal models for anxiety traits provide useful insights for the elucidation of the relevant pathophysiological mechanisms of anxiety disorders by modeling molecular pathology in a defined genetic background. However, little is currently known about the functional characteristics that distinguish high anxiety-related (HAB) from low anxiety-related (LAB) behaviors. Analytical integration of cingulate cortex (CC) synaptosomal proteomes of HAB and LAB mice revealed that the synaptic environment in the cingulate cortex of HAB animals is dominated by the stabilization and enlargement of existing excitatory dendritic spines, associated with increased high-frequency stimulation of excitatory glutamatergic synapses, enhanced control over the modulation of synaptic strength and relatively weakened inhibitory GABAergic control together with increased spontaneous synaptic activity in non-glutamatergic network members. This is coupled with increased oxidative phosphorylation (OXPHOS), enhanced fatty acid oxidation and ATP production in synaptic mitochondria. The mitochondrial effects of increased oxidative and ionic stress appear to be controlled through at least seven different mechanisms, while the mechanisms attached to the maintenance of mitochondrial structural integrity and protein homeostasis are significantly reinforced. Overall, this analysis describes a context characterized by excitatory long-term potentiation (LTP) maintenance, low de novo spine generation, significant neurotransmission imbalances and structural as well as metabolic adaptations to persistent synaptic mitochondrial Ca2+ loading and oxidative stress associated with the HAB phenotype
| Published in | American Journal of Psychiatry and Neuroscience (Volume 2, Issue 3) |
| DOI | 10.11648/j.ajpn.20140203.11 |
| Page(s) | 25-42 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2014. Published by Science Publishing Group |
Anxiety Disorders, Cingulate Cortex, Trait Anxiety Mouse Model, Proteomics, Molecular Mechanism
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APA Style
François Iris, Michaela Filiou, Christoph Wilhelm Turck. (2014). Differential Proteomics Analyses Reveal Anxiety-Associated Molecular and Cellular Mechanisms in Cingulate Cortex Synapses. American Journal of Psychiatry and Neuroscience, 2(3), 25-42. https://doi.org/10.11648/j.ajpn.20140203.11
ACS Style
François Iris; Michaela Filiou; Christoph Wilhelm Turck. Differential Proteomics Analyses Reveal Anxiety-Associated Molecular and Cellular Mechanisms in Cingulate Cortex Synapses. Am. J. Psychiatry Neurosci. 2014, 2(3), 25-42. doi: 10.11648/j.ajpn.20140203.11
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Download@article{10.11648/j.ajpn.20140203.11,
author = {François Iris and Michaela Filiou and Christoph Wilhelm Turck},
title = {Differential Proteomics Analyses Reveal Anxiety-Associated Molecular and Cellular Mechanisms in Cingulate Cortex Synapses},
journal = {American Journal of Psychiatry and Neuroscience},
volume = {2},
number = {3},
pages = {25-42},
doi = {10.11648/j.ajpn.20140203.11},
url = {https://doi.org/10.11648/j.ajpn.20140203.11},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajpn.20140203.11},
abstract = {Selectively inbred animal models for anxiety traits provide useful insights for the elucidation of the relevant pathophysiological mechanisms of anxiety disorders by modeling molecular pathology in a defined genetic background. However, little is currently known about the functional characteristics that distinguish high anxiety-related (HAB) from low anxiety-related (LAB) behaviors. Analytical integration of cingulate cortex (CC) synaptosomal proteomes of HAB and LAB mice revealed that the synaptic environment in the cingulate cortex of HAB animals is dominated by the stabilization and enlargement of existing excitatory dendritic spines, associated with increased high-frequency stimulation of excitatory glutamatergic synapses, enhanced control over the modulation of synaptic strength and relatively weakened inhibitory GABAergic control together with increased spontaneous synaptic activity in non-glutamatergic network members. This is coupled with increased oxidative phosphorylation (OXPHOS), enhanced fatty acid oxidation and ATP production in synaptic mitochondria. The mitochondrial effects of increased oxidative and ionic stress appear to be controlled through at least seven different mechanisms, while the mechanisms attached to the maintenance of mitochondrial structural integrity and protein homeostasis are significantly reinforced. Overall, this analysis describes a context characterized by excitatory long-term potentiation (LTP) maintenance, low de novo spine generation, significant neurotransmission imbalances and structural as well as metabolic adaptations to persistent synaptic mitochondrial Ca2+ loading and oxidative stress associated with the HAB phenotype},
year = {2014}
}
TY - JOUR T1 - Differential Proteomics Analyses Reveal Anxiety-Associated Molecular and Cellular Mechanisms in Cingulate Cortex Synapses AU - François Iris AU - Michaela Filiou AU - Christoph Wilhelm Turck Y1 - 2014/08/20 PY - 2014 N1 - https://doi.org/10.11648/j.ajpn.20140203.11 DO - 10.11648/j.ajpn.20140203.11 T2 - American Journal of Psychiatry and Neuroscience JF - American Journal of Psychiatry and Neuroscience JO - American Journal of Psychiatry and Neuroscience SP - 25 EP - 42 PB - Science Publishing Group SN - 2330-426X UR - https://doi.org/10.11648/j.ajpn.20140203.11 AB - Selectively inbred animal models for anxiety traits provide useful insights for the elucidation of the relevant pathophysiological mechanisms of anxiety disorders by modeling molecular pathology in a defined genetic background. However, little is currently known about the functional characteristics that distinguish high anxiety-related (HAB) from low anxiety-related (LAB) behaviors. Analytical integration of cingulate cortex (CC) synaptosomal proteomes of HAB and LAB mice revealed that the synaptic environment in the cingulate cortex of HAB animals is dominated by the stabilization and enlargement of existing excitatory dendritic spines, associated with increased high-frequency stimulation of excitatory glutamatergic synapses, enhanced control over the modulation of synaptic strength and relatively weakened inhibitory GABAergic control together with increased spontaneous synaptic activity in non-glutamatergic network members. This is coupled with increased oxidative phosphorylation (OXPHOS), enhanced fatty acid oxidation and ATP production in synaptic mitochondria. The mitochondrial effects of increased oxidative and ionic stress appear to be controlled through at least seven different mechanisms, while the mechanisms attached to the maintenance of mitochondrial structural integrity and protein homeostasis are significantly reinforced. Overall, this analysis describes a context characterized by excitatory long-term potentiation (LTP) maintenance, low de novo spine generation, significant neurotransmission imbalances and structural as well as metabolic adaptations to persistent synaptic mitochondrial Ca2+ loading and oxidative stress associated with the HAB phenotype VL - 2 IS - 3 ER -
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