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A stereological examination of neuronal and glial cell density in the dorsolateral prefrontal cortex in late-life depression

Lookup NU author(s): Dr Ahmad Khundakar, Arthur Oakley, Dr Christopher Morris, Professor Alan ThomasORCiD


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Evidence from several neuropathological studies has suggested morphological and functional deficits in key brain areas of patients with late-life depression. The dorsolateral prefrontal cortex (DLPFC) regulates mood and cognition and microstructural abnormalities have been found in the DLPFC in elderly subjects with depression (Taylor WD et al, 2004 Am J Psychiatry;161(7):1293–6). The only previous stereological investigation in older patients reported increases in neuronal density in layers 3 and 5 (Rajkowska G et al, 2005 Biol Psychiatry;58(4):297–306). This study aimed for the first time to examine changes in pyramidal and non-pyramidal neurone and glial cell volume and density in the DLPFC in late-life depression using stereological analysis in the post-mortem tissue of depressed and non-depressed elderly subjects. Brain tissue from 21 subjects (14 depressed and 7 controlled) was obtained from the Newcastle Brain Tissue Resource. The brains were fixed in 10% phosphate buffered formalin prior to DLPFC (Brodmann areas 9 and 46) excision. The tissue was embedded in paraffin and cut into 30µm-thick sections before staining with cresyl fast violet. Neuronal and glial cell densities were estimated in laminae 3 and 5, and whole cortex using a stereologically-based quantification method. Statistical analysis was performed using SPSS software using parametric testing with ANOVA. No significant differences in age, sex, pH, post mortem interval or duration of fixation were identified between groups. There was a slight, but non-significant, decrease in glial and neuronal density in the whole cortex of depressed individuals. However, after correcting for a significant negative correlation with pH, there was a trend towards significance in both glial and neuronal density in depression. Glial cell density significantly increased in layers 3 and 5 in the depressed group; however, after correction for pH, significance was not reached in layer 5 and there was only a trend towards significance in layer 3. Neuronal density or volume was not significantly altered in either layer 3 or 5. These data suggest lamina specific differences may be present in late-life depression with glial reduction, as in younger adults, offset in pyramidal cell layers by a glial cell increase which may be due to previously reported cerebrovascular disease (Thomas AJ et al, 2002 Arch Gen Psychiatry;59(9):785–92). We did not find neuronal reduction as reported in the OFC in layers 3 and 5.

Publication metadata

Author(s): Khundakar AA, Oakley AE, Morris CM, Thomas AJ

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: Journal of Psychopharmacology: BAP Summer Meeting

Year of Conference: 2007

Pages: A15

ISSN: 0269-8811

Publisher: Sage Publications Ltd.

Library holdings: Search Newcastle University Library for this item

ISBN: 14617285