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Unpredictable Chronic Mild Stress Paradigm Established Effects of Pro- and Anti-inflammatory Cytokine on Neurodegeneration-Linked Depressive States in Hamsters with Brain Endothelial Damages

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Abstract

The mechanisms by which inflammation affects the different emotional moods are only partially known. Previous works have pointed to stress hormones like glucocorticoids plus the vascular factor endothelin-1 as key factors evoking stressful states especially in relation to endothelial dysfunctions. With this work, it was our intention to establish the role of pro- and anti-inflammatory cytokine expression variations towards depression-like behaviors and consequently the development of neurodegeneration events caused by endothelial damages in the hamster (Mesocricetus auratus). Such a rodent, which is considered a valuable animal model to test depression and anxiety states, exhibited a variety of depression-like behaviors including reduction in sucrose consumption, locomotion, and exploration (p < 0.01) following exposure to unpredictable chronic mild stress. Contextually, a tight correlation between unpredictable chronic mild stress-induced depressive states and expression of the pro-inflammatory cytokines was detected as shown by marked expression levels (p < 0.01) of IL-1β and NF-kB in the hippocampus, amygdala, and prefrontal cortex. Even the anti-inflammatory cytokine IL-10 supplied notably significant (p < 0.001) expression levels in the same areas of resilient hamsters. Application of hemodynamic and endothelial functional studies pointed to altered arterial endothelial activities in depressed with respect to resilient animals. Moreover, evident damaged neuronal fields in the above areas of depressed hamsters allowed us to correlate such a behavioral phenomenon to the upregulation of IL-1β and NF-κB. Overall, the differing roles of pro- and anti-inflammatory cytokines on depressive states, especially in view of brain endothelial damages, may provide novel therapeutic measures against mood disorders linked to neurodegenerative diseases.

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Abbreviations

DEP:

Depression

RES:

Resilient

AMY:

Amygdala

PFC:

Prefrontal cortex

UCMS:

Unpredictable chronic mild stress

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Acknowledgments

We thank the Italian University Research Ministry (MIUR), Regione of Calabria (POR, FSE-2007/2013) for the financial support.

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Authors and Affiliations

  1. Comparative Neuroanatomy Laboratory of Biology, Ecology and Earth Science Department (DiBEST), University of Calabria, Ponte P. Bucci 4B, 87030, Arcavacata di Rende, Cosenza, Italy

    Ennio Avolio, Gilda Fazzari, Maria Mele, Raffaella Alò, Merylin Zizza, Wei Jiao & Marcello Canonaco

  2. Vascular Physiology Lab., Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy

    Maurizio Mandalà

  3. Department of Clinical and Experimental Medicine, University of Catanzaro “Magna Græcia”, Catanzaro, Italy

    Anna Di Vito & Tullio Barni

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  1. Ennio Avolio
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  2. Gilda Fazzari
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  3. Maria Mele
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  4. Raffaella Alò
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  10. Marcello Canonaco
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Correspondence to Ennio Avolio.

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Avolio, E., Fazzari, G., Mele, M. et al. Unpredictable Chronic Mild Stress Paradigm Established Effects of Pro- and Anti-inflammatory Cytokine on Neurodegeneration-Linked Depressive States in Hamsters with Brain Endothelial Damages. Mol Neurobiol 54, 6446–6458 (2017). https://doi.org/10.1007/s12035-016-0171-1

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