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).