Experimental Post-traumatic Stress Disorder Decreases Astrocyte Density and Changes Astrocytic Polarity in the CA1 Hippocampus of Male Rats

Abstract

Post-traumatic stress disorder (PTSD) is a psychiatric condition resulting from exposure to a traumatic event. It is characterized by several debilitating symptoms including re-experiencing the past trauma, avoidance behavior, increased fear, and hyperarousal. Key roles in the neuropathology of PTSD and its symptomatology have been attributed to the hippocampus and amygdala. These regions are involved in explicit memory processes and context encoding during fear conditioning. The aim of our study was to investigate whether PTSD is capable of altering the morphology, density and expression of glial fibrillary acidic protein (GFAP) in astrocytes from the CA1 region of the hippocampus and the medial amygdala and correlate the data obtained with the orientation index of the polarity of astrocytes. Thirty male rats were divided in two groups: control (n = 15) and PTSD (n = 15). The inescapable shock protocol, in which the animals are exposed to a single episode of footshock, was used to induce PTSD. Our results show that, in the hippocampus, PTSD is capable of decreasing the density of GFAP+ astrocytes as well as altering astrocytic morphology, as shown by the reductions observed in the total number of primary processes, in the number of primary processes in the lateral quadrants, and the degree of branching in the lateral quadrants. The analysis of the orientation index indicates that PTSD alters the polarity of hippocampal astrocytes. No alterations were observed in the amygdala astrocytes. Therefore, this study demonstrates notable changes in hippocampal astrocytes, supporting the concept that these cells play an important role in PTSD symptomatology.

Stress‐induced structural and functional modifications of astrocytes—Further implicating glia in the central response to stress

“…The study reports decreased GFAP and structural alterations in hippocampal astrocytes which were rescued with FGF2, suggesting astrocytic impairments could underlie the behavioral deficit in this model (Xia et al, ). Similar findings regarding GFAP expression and morphological alterations in astrocytes have been reported using a single inescapable foot shock protocol (Saur et al, ), indicating a conserved response by astrocytes to acute stress. We do not yet understand the impact of these structural modifications on astrocytic function at the level of the synapse.…”

Can an aversive, extinction-resistant memory trigger impairments in walking adaptability? An experimental study using adult rats

“…The aim of this study was to determine whether an aversive, extinction-resistant memory could trigger impairments in walking adaptability using a footshock paradigm to induce the aversive memory [5,[15][16][17]. Our results show that skilled walking performance score (reflecting errors in foot placement in hind and forelimbs) was reduced following extinction-resistant aversive stimuli.…”

“…After the last ladder rung walking test evaluation, animals received a lethal injection of sodic pentobarbital associated with lidocaine (10 mg/mL) (i.p.) [16].…”

“…Thus, the proposed study aims to assess, preliminarily, whether suffering an aversive experience that generates an extinction-resistant memory [5,13] can trigger impairments in walking adaptability of adult rats. [6,8,14] Inescapable footshocks (IF) are an aversive and stressful event for rodents that is widely used to model fear conditioning and aversive memory in rats [5,10,15,16]. IF has been shown to elicit dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis and the neurotransmitter systems as well as functional and/or structural changes in the hippocampus, amygdala, prefrontal cortex, locus coeruleus, and ventral tegmental area [5,13,16].…”

Glutamate dysregulation and glutamatergic therapeutics for PTSD: Evidence from human studies

“…Thus, impairment and loss of glia may also affect neuronal health [38]. Recent investigations in animal models of PTSD showed reduced astrocyte density and altered morphology in the hippocampus [44, 45]. …”