High tryptophan diet reduces CA1 intraneuronal β-amyloid in the triple transgenic mouse model of Alzheimer's disease.
Alzheimer's disease (AD) is a progressive neurodegenerative disease that impairs mnesic functions. The histopathology of the disease is manifested by the accumulation of intracellular β-amyloid (Aβ) and subsequent formation of neuritic plaques as well as the presence neurofibrillary tangles in specific brain regions associated with learning and memory including the hippocampus. Here, we analysed the effect of chronic (1 month) food diets containing low (LTrP), normal (NTrP) and high tryptophan (HTrP), 0.04, 0.20 and 0.40 g/100 g, respectively, on CA1 serotonin transporter (SERT) fibre density, intraneuronal Aβ deposition and total number of serotonergic (5-HT) neurons in an AD triple transgenic (3xTg-AD) mouse model. Nontransgenic (non-Tg) animals fed with HTrP displayed increased SERT fibre density in CA1 (35%) and in stratum lacunosum moleculare (S.Mol) (48%) compared to LTrP diet. Transgenic animals showed increased SERT fibre density in CA1 S.Mol compared to diet-matched non-Tg irrespective of dietary tryptophan content (104% for LTrP, 74% for NTrP and 35% for HTrP); no differences were observed in the total number of 5-HT neurons neither in the dorsal nor in the median raphe nuclei. However, and more relevant to AD, HTrP diet reduced intraneuronal Aβ density (by a 17%) in transgenic animals compared to transgenic animals fed with NTrP diet. Our results show that increased dietary TrP intake reduces intraneuronal Aβ load in the 3xTg-AD mouse model of AD, suggesting that enhanced TrP intake and in consequence a potential increase in 5-HT neurotransmission may be effective in reducing plaque pathology in AD.
Faculty of Life Sciences, The University of Manchester, Manchester, UK.
Harun N
HN
Noristani
Alexei
A
Verkhratsky
José J
JJ
Rodríguez
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D014364:Tryptophan / Q000008:administration & dosage*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D014364:Tryptophan