Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal

Abstract

Mounting evidence indicates that proinflammatory signaling in the brain affects mood, cognition, and behavior and is linked with the etiology of psychiatric disorders, including anxiety and depression. The purpose of this review is to focus on stress-induced bidirectional communication pathways between the central nervous system (CNS) and peripheral immune system that converge to promote a heightened neuroinflammatory environment. These communication pathways involve sympathetic outflow from the brain to the peripheral immune system that biases hematopoietic stem cells to differentiate into a glucocorticoid-resistant and primed myeloid lineage immune cell. In conjunction, microglia-dependent neuroinflammatory events promote myeloid cell trafficking to the brain that reinforces stress-related behavior, and is argued to play a role in stress-related psychiatric disorders. We will discuss evidence implicating a key role for endothelial cells that comprise the blood-brain barrier in propagating peripheral-to-central immune communication. We will also discuss novel neuron-to-glia communication pathways involving endogenous danger signals that have recently been argued to facilitate neuroinflammation under various conditions, including stress. These findings help elucidate the complex communication that occurs in response to stress and highlight novel therapeutic targets against the development of stress-related psychiatric disorders.

Stressor exposure has prolonged effects on colonic microbial community structure in Citrobacter rodentium-challenged mice

“…However, considerable psychological and physiological effects differ between the two stressors. Restraint stress is known to induce depressive-like behavior in mice, a hallmark not observed in SDR-exposed mice3738. Further, SDR is defined by activation of multiple arms of the immune response, including macrophage oxidative burst and myeloid cell trafficking, while restraint is often associated with immune repression3940.…”

(Putative) sex differences in neuroimmune modulation of memory

“…B-cells produces antibodies and are a critical part of the adaptive immune system (Haan et al, 2014). Many of these white blood cells also infiltrate into the central nervous system after immune challenge and contribute to the neuroimmune response (Weber et al, 2016). T cells ( T helper, cytotoxic, and memory cells) are critical for the adaptive immune response, and sex-biased activation of T helper (Th) cells contribute to differences between males and females in the adaptive immune response.…”

Immune signaling mechanisms of PTSD risk and symptom development: insights from animal models

“…Central inflammation can also promotes peripheral inflammation by facilitating bone marrow-induced production of monocytes and their release by the spleen, with the pro-inflammatory cytokine IL-1β facilitating the trafficking of peripheral monocytes to the brain, leading to microglial activation. Also, a severe stressor associated with physical injury can also directly promote the peripheral immune mechanisms (see Weber et al, 2016 [66] for review). Thus, microglia-derived IL-1β affects the neuronal functionality, triggering the development of PTSD-like symptoms.…”