Effects of Dexamethasone and Brain-Derived Neurotropic Factor in NT2 Cells

Stress is a major risk factor that can evoke neuropathological changes within the cortico-limbic system in neuropsychiatric, neurodegenerative, and metabolic disorders. Many of these disorders implicate the regulation of glucocorticoids (GCs) and neurotrophins, such as the brain-derived neurotropic factor (BDNF). GCs are steroidal hormones that have anti-inflammatory and immunosuppressive effects. They are widely used to treat allergy, inflammation and autoimmune diseases. The roles and functions of GCs in the central nervous system (CNS) is varied and not well understood at this time. BDNF is well known to play important roles in the survival, growth-promoting and synaptic plasticity of the CNS. However, it has also been reported that continuous exposure to BDNF results in wide spread neuronal death. While several studies have shown functional interactions between BDNF and GCs in neural events, the relationship between these interactions has not been clearly defined. The goal of this study was to determine the role (beneficial or detrimental) of a synthetic GC (dexamethasone (DEX)) and BDNF, and their effects in combination in NT2 cells (a human teratocarcinoma cell line proven to be a useful in vitro neuronal model). Our results show a decline in cell viability and proliferation in a time and dose related manner when NT2 cells were treated with DEX alone, suggesting that DEX may induce cytotoxicity genomically. In contrast, treatment with BDNF alone did not affect NT2 cell viability, probably due to the lack of BDNF receptor TrkB expression or activation in NT2 cells. Interestingly, when NT2 cells were treated with a combination of DEX and BDNF, there appeared to be greater loss of cell viability and cell proliferation compared to the treatment with DEX alone. This synergistic effect possibly occurred via the co-activation of the BDNF receptor p75 and glucocorticoid receptor common pathways that may be responsible for apoptosis and cellular death