Objectives: Bipolar disorder (BD) is a highly disabling psychiatric disorder. Studies indicate a decreased synaptic plasticity and neuronal survival in BD patients. Previously, we described a systemic pro-inflammatory/pro-oxidative status in serum of BD patients. Here we challenged differentiated human neuroblastoma SH-SY5Y cell line with serum from manic or euthymic BD patients and evaluated the potential citotoxicity.
Methods: Cells were differentiated by the combination of retinoic acid (10 µM) in medium (DMEM/F12) plus lowering FBS to 1% for 7 days of treatment. This induces the acquisition of morphological (neurite outgrowth) and biochemical (expression of tyrosine hydroxylase, neuronal nuclei protein, neuronal-specific enolase) characteristics of a dopaminergic neuron in SH-SY5Y. The FBS was replaced by inactivated serum of manic or euthymic patients and time course experiments were performed. Cellular toxicity was determined by MTT assay
Results: Cells treated with serum from manic patients showed significant decrease in viability when compared to serum from euthymic patients (p<0.05).
Conclusion: Our preliminary findings suggest that acute mood episodes induce systemic toxicity in BD, which may be due to an accumulation of deleterious substance as reactive oxygen species and pro-inflammatory cytokines. In this manner, mood episodes may be toxic to multiple cellular elements in the body, both centrally and systemically, resulting in a cumulative damage that may have multiple manifestations as impairments in neuroplasticity and cellular resilience. Support: MCT/CNPq Universal (476114/2008-0) and INCT-TM (573671/2008-7) funds.