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The immunhistochemical examination of GABAergic interneuron markers in the dorsolateral prefrontal cortex of patients with late-life depression

Published online by Cambridge University Press:  03 November 2010

Ahmad Khundakar ,
Christopher Morris  and
Alan J. Thomas
Ahmad Khundakar*
Affiliation:
Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, U.K.
Christopher Morris
Affiliation:
Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, U.K.
Alan J. Thomas
Affiliation:
Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, U.K.
*
Correspondence should be addressed to: Ahmad Khundakar, Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, U.K. Phone: +44 191 2481219; Fax: +44 191 2481101. Email: [email protected].
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Abstract

Background: The “vascular depression” hypothesis has sought to explain differences in etiology between early and late life depression, and has been reinforced by recent imaging and morphometric studies. Gamma-aminobutyric acid (GABA) is thought to play a major role in the neurobiology of depression. However, it is unclear whether there is an effect on GABA neuronal subpopulations in an elderly depressed cohort. This study therefore examined immunohistochemically two calcium-binding proteins, calretinin and parvalbumin, which have been demonstrated to bind to two distinct GABAergic interneuron subpopulations, within the dorsolateral prefrontal cortex (DLPFC) of elderly depressed patients, against age-matched controls.

Methods: Post-mortem tissue was obtained from nine controls and 11 depressed patients for the parvalbumin study and seven controls and 14 depressed patients in the calretinin study, and the mean percentage per area of immunohistochemical staining of the two antibodies was measured in individual layers and across the whole of the DLPFC.

Results: The study found a reduction in parvalbumin immunostaining in layer 6 (p = 0.05) of the DLFPC in elderly depressed patients. However, no significant changes were found in parvalbumin or calretinin immunostaining in the any other layer of the DLPFC in elderly depressed patients.

Conclusion: The study does not suggest any change in GABA interneuron subpopulations, though significant reductions in layer 6 may represent subtle disturbance in GABA parvalbumin-expressing interneuron and glumatatergic pyramidal projection neuron regulation in late-life depression.

Keywords

depressionelderlyimmunohistochemistryGABAdorsolateral prefrontal cortex
Type
Research Article
Information
International Psychogeriatrics , Volume 23 , Issue 4 , May 2011 , pp. 644 - 653
Copyright
Copyright © International Psychogeriatric Association 2010

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References

Akil, M. and Lewis, D. A. (1992). Differential distribution of parvalbumin-immunoreactive pericellular clusters of terminal boutons in developing and adult monkey neocortex. Experimental Neurology, 115, 239–249.CrossRefGoogle ScholarPubMed
Alexopoulos, G. S., Meyers, B. S., Young, R. C., Kakuma, T., Silbersweig, D. and Charlson, M. (1997). Clinically defined vascular depression. American Journal of Psychiatry, 154, 562–565.Google ScholarPubMed
Baldwin, R. C. (2005). Is vascular depression a distinct sub-type of depressive disorder? A review of causal evidence. International Journal of Geriatric Psychiatry, 20, 1–11.CrossRefGoogle ScholarPubMed
Beasley, C. L., Zhang, Z. J., Patten, I. and Reynolds, G. P. (2002). Selective deficits in prefrontal cortical GABAergic neurons in schizophrenia defined by the presence of calcium-binding proteins. Biological Psychiatry, 52, 708–715.CrossRefGoogle ScholarPubMed
Brambilla, P., Perez, J., Barale, F., Schettini, G. and Soares, J. C. (2003). GABAergic dysfunction in mood disorders. Molecular Psychiatry, 8, 721–737.CrossRefGoogle ScholarPubMed
Cotter, D. et al. (2002a). The density and spatial distribution of GABAergic neurons, labelled using calcium binding proteins, in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia. Biological Psychiatry, 51, 377–386.CrossRefGoogle Scholar
Cotter, D., Mackay, D., Chana, G., Beasley, C., Landau, S. and Everall, I. P. (2002b). Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. Cerebral Cortex, 12, 386–394.CrossRefGoogle ScholarPubMed
Gabbott, P. L., Jays, P. R. and Bacon, S. J. (1997). Calretinin neurons in human medial prefrontal cortex (areas 24a, b, c, 32′, and 25). Journal of Comparative Neurology, 381, 389–410.3.0.CO;2-Z>CrossRefGoogle Scholar
Gonzalez-Burgos, G., Krimer, L. S., Povysheva, N. V., Barrionuevo, G. and Lewis, D. A. (2005). Functional properties of fast spiking interneurons and their synaptic connections with pyramidal cells in primate dorsolateral prefrontal cortex. Journal of Neurophysiology, 93, 942–953.CrossRefGoogle ScholarPubMed
Gundersen, H. J. et al. (1988). The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. Acta Pathologica, Microbiologica et Immunologica Scandinavica, 96, 857–881.CrossRefGoogle Scholar
Herrmann, L. L., Le Masurier, M. and Ebmeier, K. P. (2008). White matter hyperintensities in late life depression: a systematic review. Journal of Neurology, Neurosurgery, and Psychiatry, 79, 619–624.CrossRefGoogle ScholarPubMed
Jacobowitz, D. M. and Winsky, L. (1991). Immunocytochemical localization of calretinin in the forebrain of the rat. Journal of Comparative Neurology, 304, 198–218.CrossRefGoogle ScholarPubMed
Khundakar, A. A. and Zetterström, T. S. (2006). Biphasic change in BDNF gene expression following antidepressant drug treatment explained by differential transcript regulation. Brain Research, 1106, 12–20.CrossRefGoogle ScholarPubMed
Khundakar, A. A., Morris, C. M., Oakley, A. E., McMeekin, W. and Thomas, A. J. (2009). Morphometric analysis of neuronal and glial cell pathology in the dorsolateral prefrontal cortex in late-life depression. British Journal of Psychiatry, 195, 163–169.CrossRefGoogle ScholarPubMed
Khundakar, A., Morris, C., Oakley, A. and Thomas, A. J. (2010). Morphometric analysis of neuronal and glial cell pathology in the caudate nucleus in late-life depression. American Journal of Psychiatry, in press.Google Scholar
Lewis, D. A. and Lund, J. S. (1990). Heterogeneity of chandelier neurons in monkey neocortex: corticotropin-releasing factor- and parvalbumin-immunoreactive populations. Journal of Comparative Neurology, 293, 599–615.CrossRefGoogle ScholarPubMed
Lewis, D. A. and Moghaddam, B. (2006). Cognitive dysfunction in schizophrenia: convergence of gamma-aminobutyric acid and glutamate alterations. Archives of Neurology, 63, 1372–1376.CrossRefGoogle ScholarPubMed
Lewis, D. A., Cruz, D. A., Melchitzky, D. S. and Pierri, J. N. (2001). Lamina-specific deficits in parvalbumin-immunoreactive varicosities in the prefrontal cortex of subjects with schizophrenia: evidence for fewer projections from the thalamus. American Journal of Psychiatry, 158, 1411–1422.CrossRefGoogle ScholarPubMed
Ongur, D., Drevets, W. C. and Price, J. L. (1998). Glial reduction in the subgenual prefrontal cortex in mood disorders. Proceedings of the National Academy of Sciences of the United States of America, 95, 13290–13295.CrossRefGoogle ScholarPubMed
Perry, E. H. (1993). Coronal Maps of Brodmann Areas in the Human Brain. London: Wolfe.Google Scholar
Rajkowska, G. et al. (1999). Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biological Psychiatry, 45, 1085–1098.CrossRefGoogle ScholarPubMed
Rajkowska, G., Miguel-Hidalgo, J. J., Dubey, P., Stockmeier, C. A. and Krishnan, K. R. (2005). Prominent reduction in pyramidal neurons density in the orbitofrontal cortex of elderly depressed patients. Biological Psychiatry, 58, 297–306.CrossRefGoogle ScholarPubMed
Rajkowska, G., O'Dwyer, G., Teleki, Z., Stockmeier, C. A. and Miguel-Hidalgo, J. J. (2007). GABAergic neurons immunoreactive for calcium binding proteins are reduced in the prefrontal cortex in major depression. Neuropsychopharmacology, 32, 471–482.CrossRefGoogle ScholarPubMed
Thomas, A. J. et al. (2000). Elevation in late-life depression of intercellular adhesion molecule-1 expression in the dorsolateral prefrontal cortex. American Journal of Psychiatry, 157, 1682–1684.CrossRefGoogle ScholarPubMed
Thomas, A. J., Ferrier, I. N., Kalaria, R. N., Perry, R. H., Brown, A. and O'Brien, J. T. (2001). A neuropathological study of vascular factors in late-life depression. Journal of Neurology, Neurosurgery, and Psychiatry, 70, 83–87.CrossRefGoogle ScholarPubMed
Thomas, A. J., Ferrier, I. N., Kalaria, R. N., Davis, S. and O'Brien, J. T. (2002a). Cell adhesion molecule expression in the dorsolateral prefrontal cortex and anterior cingulate cortex in major depression in the elderly. British Journal of Psychiatry, 181, 129–134.CrossRefGoogle ScholarPubMed
Thomas, A. J. et al. (2002b). Ischemic basis for deep white matter hyperintensities in major depression: a neuropathological study. Archives of General Psychiatry, 59, 785–792.CrossRefGoogle ScholarPubMed
Zarate, C. A. Jr. et al. (2003). Regulation of cellular plasticity cascades in the pathophysiology and treatment of mood disorders: role of the glutamatergic system. Annals of the New York Academy of Sciences, 1003, 273–291.CrossRefGoogle ScholarPubMed