Astrocyte Changes in the Prefrontal Cortex From Aged Non-suicidal Depressed Patients.

Xin-Rui Qi,Willem Kamphuis,Ling Shan

doi:10.3389/fncel.2019.00503

Abstract

Glia alterations in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) have been postulated to play an important role in the pathophysiology of psychiatric disorders. Astroglia is the most abundant type of glial cells in the central nervous system. The expression levels of astrocyte markers (glial fibrillary acidic protein (GFAP), synemin-α, synemin-β, vimentin, nestin) in isolated gray matter from postmortem ACC and DLPFC were determined to investigate the possible involvement of astrocytes in depression. Donors were aged non-suicidal subjects with bipolar disorder (BPD) or major depressive disorder (MDD), and matched controls. GFAP mRNA levels were significantly increased in the ACC of BPD patients. However, GFAP immunohistochemistry showed that the area fraction of GFAP immunoreactive astrocytes was decreased in the ACC of BPD patients, while there were no changes in the cell density and integrated optical density (IOD), indicating that there might be a reduction of GFAP-positive astrocyte processes and remodeling of the astrocyte network in BPD. Furthermore, in controls, DLPFC GFAP mRNA levels were significantly lower with a time of death at daytime (08:01–20:00 h) compared to nighttime (20:01–08:00 h). In depression, such a diurnal pattern was not present. These findings in BPD and MDD subjects warrant further studies given the crucial roles of astrocytes in the central nervous system.

Highlights

Mood disorders, such as bipolar disorder (BPD) and major depressive disorder (MDD), are common psychiatric illnesses (Ferrari et al, 2013; Bauer et al, 2018)
In the anterior cingulate cortex (ACC), there was a statistically significant increase of mRNA expression level of glial fibrillary acidic protein (GFAP) in the patients with BPD compared to controls (p = 0.018), whereas a trend for a decrease was observed in the subjects with MDD compared to controls
In the GFAP staining, we found that GFAP-ir astrocytes were mostly situated in layer I with highly ramified processes, which were distributed throughout other layers (II-VI) of the ACC (Supplementary Figure S1)

Summary

Introduction

Mood disorders, such as bipolar disorder (BPD) and major depressive disorder (MDD), are common psychiatric illnesses (Ferrari et al, 2013; Bauer et al, 2018). Infarct locations in human, and lesion experiments in animal models, the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) have been repeatedly implicated in the modulation of emotional behavior (Drevets et al, 2008a,b). Both functional changes, e.g., altered glucose metabolism and blood flow, and structural abnormalities, e.g., decreased gray matter volume of DLPFC or ACC, have been linked to the pathophysiology of mood disorders (RodríguezCano et al, 2014; Orem et al, 2019; Yang et al, 2019). Both of these were found to be abnormal or impaired in depression (Yirmiya et al, 2015; Wang et al, 2017)

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