Astrocytes in Post-traumatic Stress Disorder

Abstract

Although posttraumatic stress disorder (PTSD) is on the rise, traumatic events and their consequences are often hidden or minimized by patients for reasons linked to PTSD itself. Traumatic experiences can be broadly classified into mental stress (MS) and traumatic brain injury (TBI), but the cellular mechanisms of MS- or TBI-induced PTSD remain unknown. Recent evidence has shown that the morphological remodeling of astrocytes accompanies and arguably contributes to fearful memories and stress-related disorders. In this review, we summarize the roles of astrocytes in the pathogenesis of MS-PTSD and TBI-PTSD. Astrocytes synthesize and secrete neurotrophic, pro- and anti-inflammatory factors and regulate the microenvironment of the nervous tissue through metabolic pathways, ionostatic control, and homeostatic clearance of neurotransmitters. Stress or trauma-associated impairment of these vital astrocytic functions contribute to the pathophysiological evolution of PTSD and may present therapeutic targets.

MDMA administration attenuates hippocampal IL-β immunoreactivity and subsequent stress-enhanced fear learning: An animal model of PTSD

“…Astrocytes produce a number of pro-inflammatory cytokines ( Lau and Yu 2001 ), and this astrocyte-derived inflammation can contribute to neurological diseases ( Choi et al, 2014 ). In the pathogenesis of PTSD, changes in astrocyte morphology and neuroinflammatory functioning are involved in the development of maladaptive fear memories ( Izquierdo et al, 2016 ; Li et al 2020 ; Li et al, 2022 ). In agreement with this literature, our previous studies have demonstrated that astrocytes are mechanistically implicated in maladaptive fear responses, as the majority of IL-1β immunoreactivity, a cytokine critical to the development of SEFL, is colocalized with GFAP following severe stress ( Jones et al, 2015 ; Jones et al, 2018a ).…”

“…When examining the cellular sources of these pro-inflammatory cytokines, glial cells such as microglia and astrocytes are potential candidates, as they regulate the immune response and can release cytokines when activated ( Kim and Joh 2006 ; Cekanaviciute and Buckwalter 2016 ; Enomoto and Kato 2021 , Li et al, 2022 ). Microglia and astrocytes are also thought to be implicated in the development of PTSD, and one such mechanism may be through cytokine signaling, as they are shown to be primary cellular sources of inflammatory cytokine production following stress ( Wang et al, 2018 ; Himmerich et al, 2019 ; Johnson et al, 2019 ).…”

Neurological Manifestations of SARS-CoV2 Infection: A Narrative Review

“…A maladaptive glial response like the one previously described in neuropsychiatric pathologies was hypothesized to act as a mediator for abnormal neurological COVID-19 aftermath [ 58 ]. Another connection between long neuroCOVID and mental-health disorders could be the functional impairment of the glial cells and the tau protein, known to occur in PTSD [ 59 , 60 , 61 ].…”

Chronic ethanol consumption exacerbates future stress‐enhanced fear learning, an effect mediated by dorsal hippocampal astrocytes

“…To examine the neurobiological mechanisms underlying the effects of chronic EtOH consumption and withdrawal on SEFL, we focused on glial cells, as recent evidence suggests that glial‐ and neuroimmune‐related mechanisms contribute to both AUD and PTSD (Erickson et al, 2019; Jones, Paniccia, et al, 2018; Li et al, 2022). However, the literature reveals inconsistent changes in glial cells caused by EtOH dependence and severe stress.…”