Stress-triggered synaptic malfunction: a gate along the path from depression to dementia
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1
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Portugal
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2
Medical School, University of Athens, Department of Pharmacology, Greece
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3
Max Planck Institute of Psychiatry, Neuroadaptations Group, Germany
Clinical and experimental studies suggest a causal role of chronic stress for brain pathology and diseases e.g. depression and Alzheimer´s disease (AD) as stress is strongly associated with neuronal and synaptic atrophy/loss resulting in impaired mood and/or cognition. Indeed, synaptic loss is a key underlying pathomechanism in both disorders while growing clinical evidence supports a pathological link between depression and AD pointing to shared neurobiological underpinnings and pathogenic mechanisms e.g. AD-related mechanisms, such as APP misprocessing, are also found to be affected in depression while depression predisposes individuals to develop AD. Based on the above, our studies have been conceived to contribute towards bridging the current gap monitoring AD-related mechanisms in the CMS (chronic mild stress) animal model of depression before and after antidepressant treatment. We found that depressive status in these animals was accompanied by increased APP misprocessing and tau accumulation as well as neuronal atrophy in hippocampus and prefrontal cortex. Interestingly, antidepressant treatment with two different antidepressants reversed both biochemical and synaptic changes. Furthermore, we demonstrate the blockage of stress-triggered depressive behavior and neuronal/synaptic atrophy in animals lacking APP misprocessing and amyloid beta generation, further supporting the involvement of APP misprocessing in depressive pathology and behavior. Thus, this study forms the first in vivo approach to clarify the involvement of AD-related APP misprocessing on stress-driven synaptic pathology underlying depressive pathology.
Keywords:
chronic stress,
Depression,
Synapses,
Amyloid beta-Protein Precursor,
BACE1,
Antidepressants,
Alzheimer's disease
Conference:
4th NAMASEN Training Workshop - Dendrites 2014, Heraklion, Greece, 1 Jul - 4 Jul, 2014.
Presentation Type:
Poster presentation
Topic:
molecular pathways and signaling networks
Citation:
Sotiropoulos
I,
Lopes
S,
Morais
M,
Dalla
C,
Fernandez
P,
Almeida
OF,
Sousa
N and
Bessa
JM
(2014). Stress-triggered synaptic malfunction: a gate along the path from depression to dementia.
Front. Syst. Neurosci.
Conference Abstract:
4th NAMASEN Training Workshop - Dendrites 2014.
doi: 10.3389/conf.fnsys.2014.05.00036
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Received:
11 Apr 2014;
Published Online:
12 Jun 2014.
*
Correspondence:
Dr. Ioannis Sotiropoulos, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal, ioannis@med.uminho.pt