Astrocytes in psychotic disorder
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Feresten, Abigail Helms
issued: 2013-10-31T16:01:18Z
issued: 2013
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: 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.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/45435
note: ASTROCYTES IN PSYCHOTIC DISORDER by Abigail Helms Feresten B.A., Oberlin College, 2010 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in The Faculty of Graduate and Postdoctoral Studies (Neuroscience) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) October 2013 ? Abigail Helms Feresten, 2013 ? ii?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. 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 indica…
has type: Thesis/Dissertation
date issued: 2014-05
is shown at: 10.14288/1.0165651
language: eng
degree discipline: Neuroscience
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-ShareAlike 2.5 Canada
rights URI: http://creativecommons.org/licenses/by-nc-sa/2.5/ca/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/45435