PMID- 24140431 OWN - NLM STAT- MEDLINE DCOM- 20140722 LR - 20220330 IS - 1872-9754 (Electronic) IS - 0197-0186 (Print) IS - 0197-0186 (Linking) VI - 63 IP - 8 DP - 2013 Dec TI - Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine. PG - 756-64 LID - S0197-0186(13)00262-3 [pii] LID - 10.1016/j.neuint.2013.10.006 [doi] AB - The influence of the gut microbiota on brain chemistry has been convincingly demonstrated in rodents. In the absence of gut bacteria, the central expression of brain derived neurotropic factor, (BDNF), and N-methyl-d-aspartate receptor (NMDAR) subunits are reduced, whereas, oral probiotics increase brain BDNF, and impart significant anxiolytic effects. We tested whether prebiotic compounds, which increase intrinsic enteric microbiota, also affected brain BDNF and NMDARs. In addition, we examined whether plasma from prebiotic treated rats released BDNF from human SH-SY5Y neuroblastoma cells, to provide an initial indication of mechanism of action. Rats were gavaged with fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS) or water for five weeks, prior to measurements of brain BDNF, NMDAR subunits and amino acids associated with glutamate neurotransmission (glutamate, glutamine, and serine and alanine enantiomers). Prebiotics increased hippocampal BDNF and NR1 subunit expression relative to controls. The intake of GOS also increased hippocampal NR2A subunits, and frontal cortex NR1 and d-serine. Prebiotics did not alter glutamate, glutamine, l-serine, l-alanine or d-alanine concentrations in the brain, though GOSfeeding raised plasma d-alanine. Elevated levels of plasma peptide YY (PYY) after GOS intake was observed. Plasma from GOS rats increased the release of BDNF from SH-SY5Y cells, but not in the presence of PYY antisera. The addition of synthetic PYY to SH-SY5Y cell cultures, also elevated BDNF secretion. We conclude that prebiotic-mediated proliferation of gut microbiota in rats, like probiotics, increases brain BDNF expression, possibly through the involvement of gut hormones. The effect of GOS on components of central NMDAR signalling was greater than FOS, and may reflect the proliferative potency of GOS on microbiota. Our data therefore, provide a sound basis to further investigate the utility of prebiotics in the maintenance of brain health and adjunctive treatment of neuropsychiatric disorders. CI - Copyright (c) 2013 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Savignac, Helene M AU - Savignac HM AD - Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK. FAU - Corona, Giulia AU - Corona G FAU - Mills, Henrietta AU - Mills H FAU - Chen, Li AU - Chen L FAU - Spencer, Jeremy P E AU - Spencer JP FAU - Tzortzis, George AU - Tzortzis G FAU - Burnet, Philip W J AU - Burnet PW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131016 PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Amino Acids) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Prebiotics) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 452VLY9402 (Serine) SB - IM MH - Amino Acids/blood/metabolism MH - Animals MH - Bifidobacterium/isolation & purification MH - Body Weight MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cell Line, Tumor MH - Chromatography, High Pressure Liquid MH - Feces/microbiology MH - Frontal Lobe/metabolism MH - Hippocampus/metabolism MH - Humans MH - Male MH - *Prebiotics MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, N-Methyl-D-Aspartate/*metabolism MH - Serine/*metabolism PMC - PMC3858812 OTO - NOTNLM OT - Amino acids OT - Bifidobacteria OT - Dentate gyrus OT - Glutamate OT - HPLC OT - Western blot EDAT- 2013/10/22 06:00 MHDA- 2014/07/23 06:00 PMCR- 2013/12/01 CRDT- 2013/10/22 06:00 PHST- 2013/07/31 00:00 [received] PHST- 2013/09/24 00:00 [revised] PHST- 2013/10/10 00:00 [accepted] PHST- 2013/10/22 06:00 [entrez] PHST- 2013/10/22 06:00 [pubmed] PHST- 2014/07/23 06:00 [medline] PHST- 2013/12/01 00:00 [pmc-release] AID - S0197-0186(13)00262-3 [pii] AID - 10.1016/j.neuint.2013.10.006 [doi] PST - ppublish SO - Neurochem Int. 2013 Dec;63(8):756-64. doi: 10.1016/j.neuint.2013.10.006. Epub 2013 Oct 16.