UBC Theses and Dissertations
Astrocytes in psychotic disorder Feresten, Abigail Helms
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. I investigated whether levels of four astrocyte-specific proteins; glial fibrillary acidic protein (GFAP), aldehyde dehydrogenase type 1L1 (ALDH1L1), vimentin, and excitatory amino acid transporter type 1 (EAAT1) are altered in SCZ and BPD. Immunohistochemical staining of ALDH1L1 and GFAP in human grey and white matter was also performed, and staining patterns compared qualitatively. Relative concentrations of GFAP, ALDH1L1, vimentin, and EAAT1 were assessed post-mortem in the dorsolateral prefrontal cortex in SCZ (n=35), BPD (n=34) and non-psychiatric control (n=35) groups by western blotting. The same proteins were also quantified in the 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 in individuals with psychotic symptoms, when compared to those without. Vimentin, ALDH1L1 and EAAT1 levels did not differ between groups. Rats exposed to antipsychotics did not exhibit significant overall 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, paired with increased GFAP levels, may imply that astrocyte numbers are unchanged but astrocytes are partially activated, or may indicate a specific dysregulation of GFAP. Immunohistochemical results suggest that ALDH1L1 may be a more reliable marker of astrocytes than GFAP in human grey matter.
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