Limits...
Reduced density of glutamine synthetase immunoreactive astrocytes in different cortical areas in major depression but not in bipolar I disorder.

Bernstein HG, Meyer-Lotz G, Dobrowolny H, Bannier J, Steiner J, Walter M, Bogerts B - Front Cell Neurosci (2015)

Bottom Line: Counting of GS expressing astrocytes (ACs) and OLs in eight cortical and two subcortical brain regions of subjects with mood disorder (N = 14), BD (N = 15), and controls (N = 16) revealed that in major depression the densities of ACs were significantly reduced in some cortical but not subcortical gray matter areas, whereas no changes were found for OLs.In BD no alterations of GS-immunoreactive glia were found.From our findings we conclude that (1) GS expressing ACs are prominently involved in glutamate-related disturbances in major depression, but not in BD and (2) GS expressing OLs, though being present in significant numbers in prefrontal cortical areas, play a minor (if any) role in mood disorder pathology.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of Magdeburg Magdeburg, Germany.

ABSTRACT
There is increasing evidence for disturbances within the glutamate system in patients with affective disorders, which involve disruptions of the glutamate-glutamine-cycle. The mainly astroglia-located enzyme glutamine synthetase (GS) catalyzes the ATP-dependent condensation of ammonia and glutamate to form glutamine, thus playing a central role in glutamate and glutamine homoeostasis. However, GS is also expressed in numerous oligodendrocytes (OLs), another class of glial cells implicated in mood disorder pathology. To learn more about the role of glia-associated GS in mental illnesses, we decided to find out if numerical densities of glial cells immunostained for the enzyme protein differ between subjects with major depressive disorder, bipolar disorder (BD), and psychically healthy control cases. Counting of GS expressing astrocytes (ACs) and OLs in eight cortical and two subcortical brain regions of subjects with mood disorder (N = 14), BD (N = 15), and controls (N = 16) revealed that in major depression the densities of ACs were significantly reduced in some cortical but not subcortical gray matter areas, whereas no changes were found for OLs. In BD no alterations of GS-immunoreactive glia were found. From our findings we conclude that (1) GS expressing ACs are prominently involved in glutamate-related disturbances in major depression, but not in BD and (2) GS expressing OLs, though being present in significant numbers in prefrontal cortical areas, play a minor (if any) role in mood disorder pathology. The latter assumption is supported by findings of others showing that - at least in the mouse brain cortex - GS immunoreactive oligodendroglial cells are unable to contribute to the glutamate-glutamine-cycle due to the complete lack of amino acid transporters (Takasaki et al., 2010).

No MeSH data available.


Related in: MedlinePlus

Numerical densities of GS-expressing glial cells (ACs and OLs) in the DLPFC of subjects with MDD, BD, and controls. Compared with controls the density of GS-expressing ACs is significantly reduced in MDD cases (AC left I–III, p = 0.029; AC right I–III, p = 0.046).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4530620&req=5

Figure 2: Numerical densities of GS-expressing glial cells (ACs and OLs) in the DLPFC of subjects with MDD, BD, and controls. Compared with controls the density of GS-expressing ACs is significantly reduced in MDD cases (AC left I–III, p = 0.029; AC right I–III, p = 0.046).

Mentions: In subjects with mood disorder significantly reduced numerical densities of GS immunoreactive ACs were found the DLPFC (left side, layers I–III, p = 0.029; F = 4.487 and right side, layers I–III; p = 0.046; F = 3.647), sACC (left side, layers I–III, p = 0.021; F = 4.304), AiC (left side, layers I–III, p = 0.002; F = 7.893; right side, layers I–III, p = 0.001; F = 9.789; ride side, layers IV–VI, p = 0.015; F = 5.136). No significant changes were detectable in the pACC and the NAc. All but one (DLPCC right side, layers I–III) significant changes survived Tukey’s HSD post hoc tests. Notably, no significant alterations in the numerical densities of OLs were found. Results of the morphometric analyses are shown in Figures 2–6.


Reduced density of glutamine synthetase immunoreactive astrocytes in different cortical areas in major depression but not in bipolar I disorder.

Bernstein HG, Meyer-Lotz G, Dobrowolny H, Bannier J, Steiner J, Walter M, Bogerts B - Front Cell Neurosci (2015)

Numerical densities of GS-expressing glial cells (ACs and OLs) in the DLPFC of subjects with MDD, BD, and controls. Compared with controls the density of GS-expressing ACs is significantly reduced in MDD cases (AC left I–III, p = 0.029; AC right I–III, p = 0.046).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530620&req=5

Figure 2: Numerical densities of GS-expressing glial cells (ACs and OLs) in the DLPFC of subjects with MDD, BD, and controls. Compared with controls the density of GS-expressing ACs is significantly reduced in MDD cases (AC left I–III, p = 0.029; AC right I–III, p = 0.046).
Mentions: In subjects with mood disorder significantly reduced numerical densities of GS immunoreactive ACs were found the DLPFC (left side, layers I–III, p = 0.029; F = 4.487 and right side, layers I–III; p = 0.046; F = 3.647), sACC (left side, layers I–III, p = 0.021; F = 4.304), AiC (left side, layers I–III, p = 0.002; F = 7.893; right side, layers I–III, p = 0.001; F = 9.789; ride side, layers IV–VI, p = 0.015; F = 5.136). No significant changes were detectable in the pACC and the NAc. All but one (DLPCC right side, layers I–III) significant changes survived Tukey’s HSD post hoc tests. Notably, no significant alterations in the numerical densities of OLs were found. Results of the morphometric analyses are shown in Figures 2–6.

Bottom Line: Counting of GS expressing astrocytes (ACs) and OLs in eight cortical and two subcortical brain regions of subjects with mood disorder (N = 14), BD (N = 15), and controls (N = 16) revealed that in major depression the densities of ACs were significantly reduced in some cortical but not subcortical gray matter areas, whereas no changes were found for OLs.In BD no alterations of GS-immunoreactive glia were found.From our findings we conclude that (1) GS expressing ACs are prominently involved in glutamate-related disturbances in major depression, but not in BD and (2) GS expressing OLs, though being present in significant numbers in prefrontal cortical areas, play a minor (if any) role in mood disorder pathology.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of Magdeburg Magdeburg, Germany.

ABSTRACT
There is increasing evidence for disturbances within the glutamate system in patients with affective disorders, which involve disruptions of the glutamate-glutamine-cycle. The mainly astroglia-located enzyme glutamine synthetase (GS) catalyzes the ATP-dependent condensation of ammonia and glutamate to form glutamine, thus playing a central role in glutamate and glutamine homoeostasis. However, GS is also expressed in numerous oligodendrocytes (OLs), another class of glial cells implicated in mood disorder pathology. To learn more about the role of glia-associated GS in mental illnesses, we decided to find out if numerical densities of glial cells immunostained for the enzyme protein differ between subjects with major depressive disorder, bipolar disorder (BD), and psychically healthy control cases. Counting of GS expressing astrocytes (ACs) and OLs in eight cortical and two subcortical brain regions of subjects with mood disorder (N = 14), BD (N = 15), and controls (N = 16) revealed that in major depression the densities of ACs were significantly reduced in some cortical but not subcortical gray matter areas, whereas no changes were found for OLs. In BD no alterations of GS-immunoreactive glia were found. From our findings we conclude that (1) GS expressing ACs are prominently involved in glutamate-related disturbances in major depression, but not in BD and (2) GS expressing OLs, though being present in significant numbers in prefrontal cortical areas, play a minor (if any) role in mood disorder pathology. The latter assumption is supported by findings of others showing that - at least in the mouse brain cortex - GS immunoreactive oligodendroglial cells are unable to contribute to the glutamate-glutamine-cycle due to the complete lack of amino acid transporters (Takasaki et al., 2010).

No MeSH data available.


Related in: MedlinePlus