Gliogenesis and Glial Pathology in Depression

Abstract

Recent research has changed the perception of glia from being no more than silent supportive cells of neurons to being dynamic partners participating in brain metabolism and communication between neurons. This discovery of new glial functions coincides with growing evidence of the involvement of glia in the neuropathology of mood disorders. Unanticipated reductions in the density and number of glial cells are reported in fronto-limbic brain regions in major depression and bipolar illness. Moreover, age-dependent decreases in the density of glial fibrillary acidic protein (GFAP) -immunoreactive astrocytes and levels of GFAP protein are observed in the prefrontal cortex of younger depressed subjects. Since astrocytes participate in the uptake, metabolism and recycling of glutamate, we hypothesize that an astrocytic deficit may account for the alterations in glutamate/GABA neurotransmission in depression. Reductions in the density and ultrastructure of oligodendrocytes are also detected in the prefrontal cortex and amygdala in depression. Pathological changes in oligodendrocytes may be relevant to the disruption of white matter tracts in mood disorders reported by diffusion tensor imaging. Factors such as stress, excess of glucocorticoids, altered gene expression of neurotrophic factors and glial transporters, and changes in extracellular levels of neurotransmitters released by neurons may modify glial cell number and affect the neurophysiology of depression. Therefore, we will explore the role of these events in the possible alteration of glial number and activity, and the capacity of glia as a promising new target for therapeutic medications. Finally, we will consider the temporal relationship between glial and neuronal cell pathology in depression.Glial cells were first identified as non-neuronal elements in the nineteenth century by the anatomist R. Virchow (after [1]). At that time glia were thought to be no more than silent supportive "glue" for neurons and that glia were unable to participate in information processing. In the past two decades, research has changed this perception and provided evidence for glia being important dynamic partners of neuronal cells actively participating in brain metabolism, synaptic neurotransmission and communication between neurons [2]. The discovery of new glial functions coincides with growing evidence for the involvement of glia in the neuropathology of neurological [3] and more recently, psychiatric disorders, such as major depression and manic-depressive (bipolar) illness (reviewed in [4]) TYPES OF GLIAL CELLSGlia are the most numerous cells in the human brain, outnumbering neurons by a ratio of ten to one [5] (Fig. 1). This ratio drops to one-to-one in rodents [5,6] implying that increases in glia over neurons are associated with the progressive development of higher brain functions [7]. Although anecdotal, it is interesting that in the brain of Albert Einstein, the neuron/glia ratio in the associational parieto-temporal cortical area 39 was found to be smaller ...

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