Protective effects of high Tryptophan diet on aging-induced passive avoidance impairment and hippocampal apoptosis.

In our previous work we have shown that L-Tryptophan (TrP) enriched diet prevents the age-induced decline of hippocampal Serotonin (5-HT) production. Considering that loss or reduction in 5-HT neurotransmission may contribute to age-related cognitive decline, here we have investigated the effect of such diet on passive avoidance (PA) behavior, cell death, pro- and anti- apoptotic molecules (BAX, Bcl-2 and Caspase-3) and an important transcription factor involved in synaptic plasticity and memory (CREB). The increase in 5-HT neurotransmission in the Hippocampus (Hp) of aged rats was induced by 1 month of high TrP administration. In the first phase of our study we found that high TrP diet improves PA behaviour of aged rats and this correlated with a decrease of TUNEL positive cells in all hippocampal regions tested (CA1, CA2, CA3, DG). Interestingly, the Hp of aged animals fed with high TrP diet showed a significant downregulation of proapoptotic proteins, caspase-3 and BAX, and an increase of antiapoptotic molecules Bcl-2 as indicated by Western Blot and immunohistochemical analyses. Also, high TrP diet partially rescued the age-induced inhibition of hippocampal CREB phosphorylation. Altogether, our data suggest that enhanced TrP intake, and in consequence a potential increase in 5-HT neurotransmission, might be beneficial in preventing age-related detrimental features by inhibition of hippocampal apoptosis.