Evidence that Microglia Mediate the Neurobiological Effects of Chronic Psychological Stress on the Medial Prefrontal Cortex
Reads0
Chats0
TLDR
A role for microglia is suggested in mediating the effects of stress on PFC neuronal function and PFC-regulated behavior and the ability of a microglial activation inhibitor to alter the impact of chronic stress on these endpoints.Abstract:
Psychological stress contributes to the development of clinical depression. This has prompted many preclinical studies to investigate the neurobiology of this relationship, however, the effects of stress on glia remain unclear. In this study, we wished to determine, first, how exposure to chronic psychological stress affects microglial activity within the prefrontal cortex (PFC) and, second, whether the observed changes were meaningfully related to corresponding changes in local neuronal activity and PFC-regulated behavior. Therefore, we examined markers of microglial activation, antigen presentation, apoptosis, and persistent neuronal activation within the PFC after exposure to repeated restraint stress. We also examined the effect of stress on spatial working memory, a PFC-dependent function. Finally, we tested the ability of a microglial activation inhibitor (minocycline) to alter the impact of chronic stress on all of these endpoints. Stressor exposure produced positively correlated increases in microglial and long-term neuronal activation in the PFC but not antigen presentation or apoptosis. As expected, it also impaired spatial working memory. Importantly, minocycline reduced the impact of stress on neuronal activation and working memory, as well as microglial activation. These results suggest a role for microglia in mediating the effects of stress on PFC neuronal function and PFC-regulated behavior.read more
Citations
More filters
Journal ArticleDOI
The chronic mild stress (CMS) model of depression: History, evaluation and usage
TL;DR: An update on the validity and reliability of the CMS model, and recent data on the neurobiological basis of CMS effects and the mechanisms of antidepressant action are reviewed: the volume of this research may be unique in providing a comprehensive account of antidepressants action within a single model.
Journal ArticleDOI
Depression as a Microglial Disease
TL;DR: Some forms of depression can be considered as a microglia disease (microgliopathy), which should be treated by a personalized medical approach using microglial inhibitors or stimulators depending on the microglian status of the depressed patient.
Journal ArticleDOI
Dynamic microglial alterations underlie stress-induced depressive-like behavior and suppressed neurogenesis
Tirzah Kreisel,Matthew G. Frank,Tamar Licht,R. Reshef,O Ben-Menachem-Zidon,Michael V. Baratta,Steven F. Maier,Raz Yirmiya +7 more
TL;DR: Findings provide direct causal evidence that disturbances in microglial functioning has an etiological role in chronic stress-induced depression, suggesting that microglia stimulators could serve as fast-acting anti-depressants in some forms of depressive and stress-related conditions.
Journal ArticleDOI
The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders
Gislaine Z. Réus,Gislaine Z. Réus,Gabriel Rodrigo Fries,Laura Stertz,Marwa Badawy,Ives Cavalcante Passos,Tatiana Barichello,Flávio Kapczinski,João Quevedo +8 more
TL;DR: The role of inflammation in the pathophysiology of psychiatric disorders, such as MDD, BD, schizophrenia, and autism will be highlighted and the role of microglial activation and associated molecular cascades will be discussed as a means by which these neuroinflammatory mechanisms take place.
Journal ArticleDOI
Integrating neuroimmune systems in the neurobiology of depression
TL;DR: Interventions targeting immune-related cellular and molecular pathways may benefit subsets of MDD patients with immune dysregulation and ongoing studies examining neuroimmune mechanisms that influence neuronal activity as well as synaptic plasticity are discussed.
References
More filters
Journal ArticleDOI
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
TL;DR: Overactivated microglia can be detected using imaging techniques and therefore this knowledge offers an opportunity not only for early diagnosis but, importantly, for the development of targeted anti-inflammatory therapies that might slow or halt the progression of neurodegenerative disease.
Book
Models of Working Memory: Mechanisms of Active Maintenance and Executive Control
Akira Miyake,Priti Shah +1 more
TL;DR: This paper presents a meta-analyses of working memory from the perspective of the EPIC architecture for modelling skilled perceptual-motor and cognitive human performance and discusses the role of language, attention, and inhibitory mechanisms in this performance.
Journal ArticleDOI
The Organization of Networks within the Orbital and Medial Prefrontal Cortex of Rats, Monkeys and Humans
Dost Öngür,Joseph L. Price +1 more
TL;DR: The OMPFC appears to function as a sensory-visceromotor link, especially for eating, which appears to be critical for the guidance of reward-related behavior and for setting of mood.
Journal ArticleDOI
Stress and Depression
TL;DR: There is growing interest in moving away from unidirectional models of the stress-depression association, toward recognition of the effects of contexts and personal characteristics on the occurrence of stressors, and on the likelihood of progressive and dynamic relationships between stress and depression over time.
Journal ArticleDOI
Causal Relationship Between Stressful Life Events and the Onset of Major Depression
TL;DR: Stressed life events have a substantial causal relationship with the onset of episodes of major depression, however, about one-third of the association between stressful life events and onsets of depression is noncausal, since individuals predisposed to major depression select themselves into high-risk environments.