Clinical depression (also known as major depressive disorder or MDD) affects many people, but the biological processes that cause it (and are influenced by its treatments) are not well understood. Adult neurogenesis is a newly emerging field that could contribute to our knowledge of the etiology of depression and the effects of antidepressants. Nestin antibodies are key tools for this research, as they can be used to identify developing neurons.
Neurogenesis (generation of new neurons) takes place in the adult human brain, although only on a small scale and in certain locations, particularly within a region of the hippocampus called the dentate gyrus (DG). The neurogenesis hypothesis of depression posits that adult hippocampal neurogenesis is suppressed by stress, and is implicated in the development of depression (e.g. by increasing susceptibility); and that antidepressants increase the neurogenesis, and this is a mechanism of their action. These proposals are currently under intense debate, with different publications reporting sometimes conflicting findings (many corroborating, yet also some disputing parts of the model), and much still to be learned. As the evidence builds, it seems that there is an overall trend of stress down-regulating neurogenesis and antidepressant drugs (and other treatments) up-regulating it, but with notable exceptions. Furthermore, the significance of these effects to the symptoms of depression is yet to be determined.
Nestin is well known as useful marker for researching adult neurogenesis and its role in depression. Animal studies have found that, within the dentate gyrus, nestin is expressed during early stages of neurogenesis, when the developing neurons are classed as Type 1 (quiescent) and then Type 2 (amplifying) cells. Type 1 cells are radial-glia-like stem cells; each divides asymmetrically to generate a Type 2 cell and a Type 1 cell. Type 2 cells are called neural progenitor cells (NPCs), and unlike Type 1 cells, do not express the marker GFAP. As the neurogenesis process continues, the NPCs develop into neuroblasts, and eventually mature granule cells (neurons).
IF analysis of Nestin in PC-3 cells
In a seminal paper (with human rather than animal subjects), Boldrini et al. investigated neurogenesis in antidepressant-treated and untreated people with major depressive disorder, and non-depressed controls. For example, the researchers looked for NPCs in the DG of the hippocampus. Brain sections were immunostained with a nestin antibody and antibodies for other relevant markers, either individually or in combination (e.g. nestin plus GFAP). The amplifying NPCs were identified as staining for nestin (termed ‘nestin-immunoreactive’ or nestin-IR) but not GFAP (although in this human study, nestin-IR and GFAP-IR cells were observed to be largely separate populations), and with the morphology of this cell type (different from the quiescent stage). It was discovered that, on average, individuals with MDD treated with antidepressants did have a higher number of NPCs than the untreated MDD group, though also the controls. The next steps could be to establish if the level of NPC proliferation is correlated to antidepressant efficacy; if so, then this could help guide future drug development.
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Written by Carly Hammond
