It remains to be determined whether the cellular pathology is the reason for, or the consequence of, depression. Functional implications of glial abnormalities in depression The glial cells analyzed in the above studies do not represent a homogeneous population of cells. Glial cells are composed of distinct populations of oligodendrocytes, microglia, and astrocytes. The Inhibitors,research,lifescience,medical crucial role of glial cell types in brain function is currently being reevaluated.

In addition to their traditional roles in neuronal migration (radial glia), myelin formation (oligodendrocytes), and inflammatory processes (astrocytes and microglia), glia (predominantly astrocytes) are now thought to provide trophic support to neurons, neuronal metabolism, and the formation of synapses and neurotransmission.15 The three distinct glial cell types cannot be identified in the previously mentioned studies as those tissues were Inhibitors,research,lifescience,medical stained for Nissl substance and such staining does not distinguish reliably between types of glial cells. Nissl staining only reveals morphological features of glial cell bodies and not glial cell processes. On the other hand, recent irnmunohistochemical examination of glial fibrillary acidic protein (GFAP), a marker of reactive astroglia, in Inhibitors,research,lifescience,medical the dorsolateral prefrontal cortex implicates

astrocytes in the overall glial pathology in MDD.68 Although no significant group differences in the packing Enzastaurin density of GFAP-reactive astrocytes are present Inhibitors,research,lifescience,medical in this study, there is a significant correlation between age and GFAP immunoreactivity among subjects with MDD, when the entire group of MDD (young and old) is compared with normal controls. A significant reduction in the population of reactive astroglia is found in a small subgroup of young (30 to 45 years old)

subjects with MDD, as compared to young control subjects and older (46 to 86 years old) subjects with MDD (Figures 3A and 3B). This subgroup of younger adults with MDD also had a shorter duration of depression and most of these subjects were suicide victims. Recent observations from our laboratory Inhibitors,research,lifescience,medical confirm that the levels of GFAP protein are also reduced in these first young adults with MDD as compared to age-matched control subjects (Figures 3C and 3D), and that GFAP levels are positively correlated with age at the time of death and with the age of onset of depression.69 Thus, the involvement of GFAP expression in early- versus late-life depression differs because the underlying pathophysiology in early-life depression is different from that in late-life depression. Clinical evidence confirms that late-onset depression (first depressive episode when older than 50 years) differs from early-onset depression by its etiology, phenomenology, and cerebrovascular pathology.70-72 Figure 3. An illustration of the pathology of glial cells found in the dorsolateral prefrontal cortex in MDD.