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. 2007 Feb;32(2):471-82.
doi: 10.1038/sj.npp.1301234. Epub 2006 Oct 25.

GABAergic neurons immunoreactive for calcium binding proteins are reduced in the prefrontal cortex in major depression

Grazyna Rajkowska  1 , Gillian O'Dwyer, Zsofia Teleki, Craig A Stockmeier, Jose Javier Miguel-Hidalgo
Affiliations

GABAergic neurons immunoreactive for calcium binding proteins are reduced in the prefrontal cortex in major depression

Grazyna Rajkowska et al. Neuropsychopharmacology. 2007 Feb.

Abstract

Post-mortem morphometric studies report reductions in the average density and size of cortical neurons in the dorsolateral prefrontal cortex (dlPFC) and orbitofrontal cortex (ORB) in major depressive disorder (MDD). The contribution of specific neuronal phenotypes to this general pathology in depression is still unclear. Post-mortem sections from the dlPFC and ORB regions of 14 subjects with MDD and 11 controls were immunostained to visualize calbindin-immunoreactive (CB-IR) and parvalbumin-immunoreactive (PV-IR) presumptive GABAergic neurons. A three-dimensional cell counting probe was used to assess the cell packing density and size of CB-IR neurons in layers II+IIIa and PV-IR neurons in layers III-VI. The density of CB-IR neurons was significantly reduced by 50% in depression in the dlPFC and there was a trend toward reduction in the ORB. The size of CB-IR somata was significantly decreased (18%) in depression in the dlPFC with a trend toward reduction in the ORB. In contrast, there was no difference in the density of PV-IR neurons between the depressed and control groups in the dlPFC. The size of PV-IR neuronal soma was unchanged in depressed compared to control subjects in either dlPFC or ORB. In depression, subpopulations of GABAergic neurons may be affected differently in dlPFC and ORB. A significant reduction in the density and size of GABAergic interneurons immunoreactive for calcium binding proteins was found predominantly in the dlPFC region. These cellular changes are consistent with recent neuroimaging studies revealing a reduction in the cortical levels of GABA in depression.

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Figures

Figure 1
Figure 1
Comparison of the cell packing density of CB-IR (a and c) and PV-IR (b and d) neurons in Brodmann's areas 9 and 47 (see the middle picture for the localization of these areas) of control subjects and subjects with MDD. A significant 50% reduction in the density of CB-IR neurons in Brodmann's area 9 in MDD subjects (a) and a 27% trend toward a reduction in CB-IR (c) and PV-IR neurons (d) in Brodmann's area 47 are illustrated. Values for the individual subjects (circles) and mean values (horizontal lines) are given without the adjustment for the covariates.
Figure 2
Figure 2
Photomicrographs of one pair of age-matched control and MDD subjects showing CB (a and b) and PV (c and d) immunoreactive neurons in the upper two-thirds of the cortical width in Brodmann's area 9 of the dlPFC. Note that CB-IR neurons are localized in upper cortical layers II + IIIa (a and b), whereas PV-IR neurons are more numerous and have a wider distribution across middle and lower cortical layers III–VI (c and d). Although adjacent sections from area 9 were used for each of the markers, there is a 50% reduction in CB-IR neurons in MDD as compared to control subjects, whereas no differences in PV-IR neurons were observed between the groups. Images were obtained using the × 4 objective, scale bar = 125 μm.
Figure 3
Figure 3
Scatter plot illustrating the relationship between the density of CB-IR neurons in area 9 and age at the time of death. Note that the density of CB-IR neurons was significantly inversely correlated with age in the MDD group but not in the control group.
Figure 4
Figure 4
Scatter plots demonstrating the significant positive correlation between density of PV-IR neurons in area 47 and tissue pH in the MDD group. Similar correlation was not observed in the control group.
See this image and copyright information in PMC

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References

    1. Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A, Bunney WE, et al. Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry. 1995;52:258–266. - PubMed
    1. Aznar S, Qian Z, Shah R, Rahbek B, Knudsen GM. The 5-HT1A serotonin receptor is located on calbindin- and parvalbumin-containing neurons in the rat brain. Brain Res. 2003;959:58–67. - PubMed
    1. Baimbridge KG, Celio MR, Rogers JH. Calcium-binding proteins in the nervous system. Trends Neurosci. 1992;15:303–308. - PubMed
    1. Balestrino M, Somjen GG. Concentration of carbon dioxide, interstitial pH and synaptic transmission in hippocampal formation of the rat. J Physiol. 1988;396:247–266. - PMC - PubMed
    1. Beasley C, Reynolds G. Parvalbumin-immunoreactive neurons are reduced in the prefrontal cortex of schizophrenics. Schizophr Res. 1997;24:349–355. - PubMed

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