.. Alterations in GFAP in both BPD and M.DD arc also suggested by a proteomic study in which different forms of GFAP proteins displayed disease-specific abnormalities.73 Oligodendrocytes may also be involved in the cellular pathology of depression. In both the dorsolateral prefrontal and anterior frontal cortex in subjects with BPD or MDD, there are ultrastructural changes in oligodendrocytes and there is a reduction in the density and immunoreactivity of these

cells.74,75 Moreover, key oligodendrocyte-related Inhibitors,research,lifescience,medical and myelin-related gene expression is reduced in the dorsolateral prefrontal cortex in BPD.76 While these results are intriguing, further immunohistochemical and molecular studies are needed to definitively determine which specific glial cell types are compromised in BPD and whether the same or different Inhibitors,research,lifescience,medical types of glial cells are involved in the pathology reported in MDD. Reductions in glial number and density, in addition to changes in size and shape, might, be related to the dysfunction of monoamine and glutamate systems reported extensively in depression. For example, astrocytes express virtually all of the receptor systems,

ion channels, and Inhibitors,research,lifescience,medical transporters found in neurons.15 Thus, the postsynaptic monoaminergic receptors distributed on glial cell bodies and processes may play a role in serotonin, norepinephrine, or dopamine neurotransmission. Moreover, astroglia are the primary sites of glutamate uptake by glial transporters and are important in regulating NMDA receptor activity. Astroglia regulate the levels of extracellular glutamate and thereby Inhibitors,research,lifescience,medical protect neurons in vitro from cell death and provide energy for neurons. Astrocytic

pathology in MDD may indirectly promote glutamate-mediated neuronal excitotoxiclty, with consequences that may be detected by functional neuroimaging. A mounting body of data suggests that treatment with antidepressant or mood-stabilizing medications regulates neuronal survival and also influences neurogenesis. Pharmacologically induced increases in neurogenesis in adult rodent brain have been reported in two independent studies.77,78 Moreover, there is evidence that Inhibitors,research,lifescience,medical treatment with lithium induces an increase in the astrocytic Resminostat protein GFAP in rodent hippocampus79,80 and the neural lobe of the pituitary.81 However, whether these increases represent a BTK animal study protective or compensatory effect of these medications, and the mechanisms underlying the regulation of neurogenesis and glial proliferation have to be further investigated. Furthermore, a precise link between cell loss and atrophy, observed in the postmortem human brain, and medication-induced production of new cells, observed in the animal brain, has yet to be established. Limitations in postmortem pathology studies in mood disorders Postmortem studies cannot yet clearly define whether a true loss of cells underlies prominent reductions in cell density and size detected in mood disorders.