Increased expression of glial fibrillary acidic protein in prefrontal cortex in psychotic illness

Feresten, Abigail H; Barakauskas, Vilte; Ypsilanti, Athéna R.; Barr, Alasdair M.; Beasley, Clare L.

doi:10.1016/j.schres.2013.07.024

Cited by 74 publications

(59 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We used a comprehensive range of measures, mRNA and protein expression of GFAP as well as classification of astrocyte morphology based on GFAP immunostaining. The measures were internally consistent with one another and confirmed previously noted correlations between GFAP expression and age (positive; Nichols et al, 1993) and tissue pH (negative; Feresten et al, 2013;Toro et al, 2006), supporting the internal validity of our study as well as the results of earlier studies.…”

Section: Discussionsupporting

confidence: 89%

Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Catts

Wong

Fillman

et al. 2014

Aust N Z J Psychiatry

130

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 89%

Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Catts

Wong

Fillman

et al. 2014

Aust N Z J Psychiatry

130

View full text Add to dashboard Cite

show abstract

“…Neither the number of cells expressing ALDH1L1 (Supplementary Figure S1G) nor ALDH1L1 protein expression (Supplementary Figure S1H) changed in the NAcore following EtOH self-administration. This is in agreement with an immunoblotting study of schizophrenic brain samples, which found increased GFAP expression, but no change in ALDH1L1 expression compared to controls (Feresten et al, 2013). In contrast, Supplementary Figure S1I indicates that glutamine synthetase expression increased in the NAcore after 3 weeks abstinence from EtOH.…”

Section: Nacore Gfap þ Astrocyte Density Increased After 3 Weeks Abstsupporting

confidence: 90%

Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence

Bull

Freitas

Zou

et al. 2014

Neuropsychopharmacol

124

106

View full text Add to dashboard Cite

Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH selfadministration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with astrocyte-specific DREADDs. Taken together, our findings demonstrate that NAcore astrocytes can shape the motivation to self-administer ethanol; suggesting that the development of ligands which selectively stimulate astrocytes may be a successful strategy to abate ethanol-seeking behavior.

show abstract

“…The intensity of each band of interest was normalized both to the average band intensity of the adjacent pooled standards (to account for blottoblot variability) and to the total protein stain for that lane (to account for variations in sample loading and transfer), as previously described. 27 Samples were run twice on different days, resulting in a betweenrun correlation of r = 0.84, with mean values used for analysis.…”

Section: Quantification Of Oligodendrocyte-associated Proteinsmentioning

confidence: 99%

Evidence for morphological alterations in prefrontal white matter glia in schizophrenia and bipolar disorder

Hercher

Chopra

Beasley

2014

jpn

Self Cite

138

112

View full text Add to dashboard Cite

Increased expression of glial fibrillary acidic protein in prefrontal cortex in psychotic illness

Cited by 74 publications

References 42 publications

Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation

Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence

Evidence for morphological alterations in prefrontal white matter glia in schizophrenia and bipolar disorder

Contact Info

Product

Resources

About