Thiamine Deficiency and Neuronal Calcium Homeostasis

Figure 34.1 Thiamine deficiency (TD) increased intracellular calcium concentration in in cultured cortical neurons. Cortical neurons were isolated from the cerebral cortex of mice and maintained in vitro for seven days (DFV7). TD was induced in these neurons by the treatment of amprolium (1 mmol/L) for one or four days (TDl or TD4). The intracellular calcium concentration was measured. Short-term TD (TDl) had little effect on calcium homeostasis longer duration of TD (TD4) caused a significant increase in intracellular calcium concentration. The results are the mean SEM of three repeated experiments.

We have previously demonstrated that thiamine deficiency induces ER stress or unfolded protein response (UPR) in animals and in cultured neurons (Wang et al. 2007). ER stress refers to the accumulation of unfolded or misfolded proteins in the ER lumen, resulting in an overall decrease in translation, enhanced protein degradation and increased levels of ER chaperones, which consequently increases the protein folding capacity of the ER. Sustained ER stress ultimately leads to the apoptotic death of the cell (Xu et al. 2005). A major cause of ER stress is the perturbation of calcium homeostasis (Matus et al. 2011). Therefore, it is likely that TD-induced alterations in [Ca ]i causes ER stress. 

---