Palmitic acid increases apoptosis of neural stem cells via activating c-Jun N-terminal kinase

Elevated plasma free fatty acid (FFA) level is common in many pathological conditions, including neurological disorders, and their deleterious effects on various cells have been well documented. However, it remains to be investigated whether elevated FFAs would have a direct effect on neural stem cells (NSCs). Here, we reported that palmitic acid (PA) impaired cell viability and increased apoptosis of NSCs significantly in a dose- and time-dependent manner. Increased protein levels of Bax and cleaved caspase 3 coupled with decreased expression of Bcl-2 were also observed in NSCs with increasing dose or time of PA treatment, whereas caspase 3 expression remained relatively unaltered. In parallel to this, the expression of phospho-c-Jun N-terminal kinase (p-JNK) in NSCs challenged with PA was increased significantly; however, JNK expression appeared stable. Remarkably, JNK inhibitor effectively reduced the apoptosis of NSCs induced by PA. The expression of phospho-p38 (p-p38), p38, phospho-extracellular regulated protein kinases 1/2 (p-EKR1/2) and EKR1/2 in NSCs was not affected by PA treatment. In consideration of the above, it is suggested that elevated plasma FFA level may induce apoptosis of NSCs in vivo, and that this might be one of possible underlying mechanisms for the cognitive disturbance in neurological disorders.