Abstract
Hyper activation of the neuroimmune system is strongly related to the development of neuropsychiatric disorders. Psychosocial stress has been postulated to play an important role in triggering anxiety and major depression. In preclinical models, there is mounting evidence that social defeat stress activates microglial cells in the central nervous system. This type of stress could be one of the major factors in the development of these psychopathologies. Here, we reviewed the most recent literature on social defeat and the associated immunological reactions. We focused our attention on microglial cells and kept the effect of social defeat over microglia separate from the effect of this stressor on other immune cells and the influence of peripheral immune components in priming central immune reactions. Furthermore, we considered how social defeat stress affects microglial cells and the consequent development of anxiety- and depressive-like states in preclinical studies. We highlighted evidence for the negative impact of the over-activation of the neuroimmune system, especially by the overproduction of pro-inflammatory mediators and cytotoxins. Overproduction of these molecules may cause cellular damage and loss or decreased function of neuronal activity by excessively pruning synaptic connections that ultimately contribute to the development of anxiety- and depressive-like states.
Highlights
Neuropsychiatric disorders, such as anxiety and major depression (MD), are highly prevalent and contribute significantly to the worldwide burden of diseases (Ferrari et al, 2013; Whiteford et al, 2013)
↑ latency to enter the center in the OFT at 0.5 and 8 days ↓ time spent in the center in the OFT at 0.5 days ↓ time spent in the interaction zone in the SAT at 0.5, 8 and 24 days ↑ time spent in the corners in the SAT at 0.5 and 24 days ↓ % time spent in the interaction zone in the SAT ↑ latency to enter the center in the OFT after repeated social defeat (RSD) (3 and 6 days) ↓ time spent in the center in the OFT after RSD (3 and 6 days) ↓ time to enter the dark zone in the L/D box after RSD (6 days) ↓ time spent in the light zone in the L/D box after RSD (6 days)
The social defeat (SD) paradigm is an important tool to induce anxiety- and depressive-like states in laboratory animals for investigating stress-induced immunological and behavioral alterations. It seems that the development of anxiety and MD is, besides microglial activation, dependent on peripheral monocyte recruitment to the brain (McKim et al, 2016b), attaching importance to the bidirectional communication between the brain and peripheral immune system
Summary
Neuropsychiatric disorders, such as anxiety and major depression (MD), are highly prevalent and contribute significantly to the worldwide burden of diseases (Ferrari et al, 2013; Whiteford et al, 2013). Inflammatory processes are usually self-limited, culminating with tissue repair; damage to the CNS occurs when the system is over-activated for a long time, extending the release of pro-inflammatory mediators and neurotoxins This process can worsen tissue damage and negatively impact disease outcome, leading to anxiety- and depressive-like states (Reader et al, 2015; Ramirez and Sheridan, 2016). M1-polarized microglia are associated with the production of pro-inflammatory cytokines such as tumor necrosis factorα (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), superoxide, nitric oxide, reactive oxygen species and proteases (Ajmone-Cat et al, 2013), whereas M2-polarized microglia express cytokines and receptors that are implicated in the inhibition of inflammation and restoration of homeostasis by tissue repair and extracellular matrix reconstruction (Nakagawa and Chiba, 2014; Tang and Le, 2016) As this nomenclature is not fully accepted and some authors consider microglia polarization to have derived from studying peripheral macrophages rather than microglia (Ransohoff, 2016), it is important to carefully use and interpret these terms to avoid misunderstandings
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
