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

Brain Res Bull. 2017 Jan:128:76-82. doi: 10.1016/j.brainresbull.2016.11.007. Epub 2016 Nov 23.

Abstract

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.

Keywords: Apoptotic molecules; CREB; Hippocampus; Learning; Serotonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Aging / pathology*
  • Aging / psychology*
  • Animal Feed
  • Animals
  • Apoptosis* / physiology
  • Avoidance Learning* / physiology
  • Caspase 3 / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Dietary Supplements
  • Hippocampus / pathology*
  • Hippocampus / physiology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Random Allocation
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Tryptophan / administration & dosage*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, rat
  • Bcl2 protein, rat
  • Cyclic AMP Response Element-Binding Protein
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Serotonin
  • Tryptophan
  • Casp3 protein, rat
  • Caspase 3