title: Increased expression of glial fibrillary acidic protein in prefrontal cortex in psychotic illness.
abstract: Astrocyte dysregulation has been implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BPD), however the exact nature of astrocytic alterations remains to be identified. In this study we investigated whether levels of four astrocyte-specific proteins; glial fibrillary acidic protein (GFAP), aldehyde dehydrogenase 1L1 (ALDH1L1), vimentin and excitatory amino acid transporter 1 (EAAT1) are altered in SCZ and BPD. Relative concentrations of GFAP, ALDH1L1, vimentin and EAAT1 were assessed post-mortem in dorsolateral prefrontal cortex in SCZ (n=35), BPD (n=34) and non-psychiatric controls (n=35) by western blotting. The same proteins were also quantified in cingulate cortex of rats administered the antipsychotics haloperidol and clozapine. Elevated levels of GFAP were observed in SCZ and BPD, when compared to controls. GFAP was also significantly increased when comparing individuals with psychotic symptoms against those without. Vimentin, ALDH1L1 and EAAT1 levels did not differ between groups. Rats exposed to antipsychotics did not exhibit significant differences in any astrocytic protein, suggesting that increased GFAP in SCZ is not attributable to antipsychotic treatment. Our findings indicate that astrocyte pathology may be associated with psychotic symptoms. Lack of ALDH1L1 and vimentin variability and increased GFAP levels may imply that astrocyte numbers are unchanged but astrocytes are partially activated, or may indicate a specific dysregulation of GFAP.
authors.affiliation: Department of Psychiatry, University of British Columbia, Vancouver, Canada.
authors.forename: Abigail H
authors.initials: AH
authors.lastname: Feresten
authors.forename: Vilte
authors.initials: V
authors.lastname: Barakauskas
authors.forename: Athena
authors.initials: A
authors.lastname: Ypsilanti
authors.forename: Alasdair M
authors.initials: AM
authors.lastname: Barr
authors.forename: Clare L
authors.initials: CL
authors.lastname: Beasley
mesh_terms: D000328:Adult; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001714:Bipolar Disorder / Q000473:pathology; D016009:Chi-Square Distribution; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D000587:Oxidoreductases Acting on CH-NH Group Donors; D017397:Prefrontal Cortex / Q000378:metabolism*; D011618:Psychotic Disorders / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014746:Vimentin / Q000378:metabolism; D000099295:Formyltetrahydrofolate Dehydrogenase
chemical_list: D000444:Aldehyde Dehydrogenase; D014150:Antipsychotic Agents; D027341:Excitatory Amino Acid Transporter 1; D005904:Glial Fibrillary Acidic Protein; D000587:Oxidoreductases Acting on CH-NH Group Donors; D014746:Vimentin; D000099295:Formyltetrahydrofolate Dehydrogenase; C493394:SLC1A3 protein, human
keywords: Aldehyde dehydrogenase; Antipsychotic; Astrocyte; Bipolar disorder; Schizophrenia; Vimentin