Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Abstract

Objective: While schizophrenia may have a progressive component, the evidence for neurodegenerative processes as indicated by reactive astrocytes is inconclusive. We recently identified a subgroup of individuals with schizophrenia with increased expression of inflammatory markers in prefrontal cortex, and hypothesized that this subgroup would also have reactive astrocytes. Method:We measured glial fibrillary acidic protein (GFAP) mRNA by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) and protein levels by immunoblotting in grey matter homogenate from 37 individuals with schizophrenia and 37 unaffected controls. We examined the morphology of GFAP-positive astrocytes in immunostained sections of middle frontal gyrus. We tested if GFAP expression or astrocyte morphology were altered in people with schizophrenia with increased expression of inflammatory markers. We used RNA-Seq data on a subset of patients and controls (n=20/group) to ascertain whether mRNA transcripts associated with astrogliosis were elevated in the individuals with active neuroinflammation.Results: GFAP (mRNA and protein) levels and astrocyte morphology were not significantly different between people with schizophrenia and controls overall. However, individuals with schizophrenia with neuroinflammation had increased expression of GFAP mRNA (t(33)=2.978, p=0.005), hypertrophic astrocyte morphology (χ 2 (2)=6.281, p=0.043), and statistically significant elevated expression of three mRNA transcripts previously associated with astrogliosis. Conclusions:We found clear evidence of astrogliosis in a subset of people with schizophrenia. We suggest that the lack of astrogliosis reported in previous studies may be due to cohort differences in aetiopathology, illness stage, treatment exposure, or a failure to examine subsets of people with schizophrenia.

Nuclear Receptors and Neuroinflammation in Schizophrenia

“…Previous work from our group has demonstrated reduced cognitive performance in individuals with schizophrenia with high inflammation [60], thus it appears that high inflammatory peripheral activity may have functional consequences for the brain. Here, our data do not support the hypothesis that decreased signalling via lower retinoid receptor levels is a likely contributor to the high inflammation in schizophrenia, but in fact we find increased retinoid receptors in high inflammation schizophrenia, perhaps reflecting an attempt to compensate for putative tissue damage during neuroinflammatory processes, as suggested by grey matter volume reductions [46] and elevated astrogliosis in those with schizophrenia and high inflammation [61]. …”

Neuroinflammation in Schizophrenia Focused on the Pharmacological and Therapeutic Evidence

“…If go further, we may suggest that astroglial histopathology exists in part or a subgroup of schizophrenia patients. This suggestion coincides with the report in a recent study with clear evidence of astrogliosis in a subset of people with schizophrenia 52 .…”

Gunn rats with glial activation in the hippocampus show prolonged immobility time in the forced swimming test and tail suspension test

“…Recent studies imply that glial activation plays a role in the pathogenesis of psychiatric disorders, such as schizophrenia (Bernstein, Steiner, Guest, Dobrowolny, & Bogerts, 2015; Catts, Wong, Fillman, Fung, & Shannon Weickert, 2014) and major depression (Stockmeier et al., 2004; Torres‐Platas, Cruceanu, Chen, Turecki, & Mechawar, 2014), even though very little is known about their pathophysiology. In particular, several postmortem brain studies indicate that activated microglia are involved in both schizophrenia (Steiner et al., 2006) and major depression (Bayer, Busleia, Havasb, & Falkaia, 1999; Steiner et al., 2011).…”