Neonatal prebiotic (BGOS) supplementation increases the levels of synaptophysin, GluN2A-subunits and BDNF proteins in the adult rat hippocampus.

Published on Mar 1, 2016in Synapse2.545
· DOI :10.1002/syn.21880
Sarah H. Williams2
Estimated H-index: 2
(University of Oxford),
Li Chen6
Estimated H-index: 6
(University of Oxford)
+ 3 AuthorsPhilip W.J. Burnet31
Estimated H-index: 31
(University of Oxford)
Compelling data suggest that perturbations in microbial colonization of the gut in early-life, influences neurodevelopment and adult brain function. If this is the case, then ensuring the growth of beneficial bacteria at an early age will lead to optimal brain development and maturation. We have tested whether feeding neonatal rats daily (from post-natal days 3-21) with a galacto-oligosaccharide prebiotic (Bimuno®, BGOS) or a control solution, alters the levels of hippocampal N-Methyl-D-Aspartate receptor (NMDAR) subunits (GluN1, GluN2A, GluN2B), synaptic proteins (synaptophysin, MAP2, and GAP43) and brain-derived-neurotrophic factor (BDNF), at post-natal days 22 and 56. The administration of BGOS significantly elevated GluN2A subunits, synaptophysin and BDNF in the hippocampus of 22 day old rats. The effect was also observed on day 56 (26 days after the feeding ceased). The levels of all other proteins (GluN1, GluN2B, MAP2, GAP43) remained unaltered. Increased GluN2A, synaptophysin, BDNF, but not MAP2, may suggest that neonatal BGOS feeding alters neurotransmission rather than synaptic architecture. Although the functional consequences of our findings require further investigation, the current study confirms that the manipulation of gut bacteria in early-life, has central effects that persist until at least young adulthood.
  • References (18)
  • Citations (28)
📖 Papers frequently viewed together
119 Citations
78 Citations
1,199 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Hélène M. Savignac (UCC: University College Cork)H-Index: 12
#2Mónica Tramullas (UCC: University College Cork)H-Index: 13
Last. John F. Cryan (UCC: University College Cork)H-Index: 91
view all 5 authors...
Increasing evidence suggests that a brain–gut–microbiome axis exists, which has the potential to play a major role in modulating behaviour. However, the role of this axis in cognition remains relatively unexplored. Probiotics, which are commensal bacteria offering potential health benefit, have been shown to decrease anxiety, depression and visceral pain-related behaviours. In this study, we investigate the potential of two Bifidobacteria strains to modulate cognitive processes and visceral pain...
122 CitationsSource
#1Kristin Schmidt (Warneford Hospital)H-Index: 2
#2Philip J. Cowen (Warneford Hospital)H-Index: 78
Last. Philip W.J. Burnet (Warneford Hospital)H-Index: 31
view all 6 authors...
Rationale There is now compelling evidence for a link between enteric microbiota and brain function. The ingestion of probiotics modulates the processing of information that is strongly linked to anxiety and depression, and influences the neuroendocrine stress response. We have recently demonstrated that prebiotics (soluble fibres that augment the growth of indigenous microbiota) have significant neurobiological effects in rats, but their action in humans has not been reported.
148 CitationsSource
#1Fanny B. MorelH-Index: 2
#2Raish OozeerH-Index: 15
Last. Catherine MichelH-Index: 17
view all 8 authors...
Abstract Objective Increasing evidence suggests that early nutrition has programming effects on adult health. Identifying mechanisms underlying nutritional programming would aid in the design of new disease prevention strategies. The intestinal microbiota could be a key player in this programming because it affects host metabolic homeostasis, postnatal gut colonization is sensitive to early nutrition, and initial microbial set-up is thought to shape microbiota composition for life. The aim of th...
17 CitationsSource
#1Abigail Mariga (NYU: New York University)H-Index: 4
#2Jiri Zavadil (IARC: International Agency for Research on Cancer)H-Index: 46
Last. Moses V. ChaoH-Index: 96
view all 4 authors...
Neurotrophins play a crucial role in mediating neuronal survival and synaptic plasticity. A lack of trophic factor support in the peripheral nervous system (PNS) is associated with a transcription-dependent programmed cell death process in developing sympathetic neurons. While most of the attention has been on events culminating in cell death in the PNS, the earliest events that occur after trophic factor withdrawal in the central nervous system (CNS) have not been investigated. In the CNS, brai...
25 CitationsSource
#1Yuliya E. Borre (UCC: University College Cork)H-Index: 8
#2Gerard W. O'Keeffe (UCC: University College Cork)H-Index: 24
Last. John F. Cryan (UCC: University College Cork)H-Index: 91
view all 6 authors...
Gut microbiota is essential to human health, playing a major role in the bidirectional communication between the gastrointestinal tract and the central nervous system. The microbiota undergoes a vigorous process of development throughout the lifespan and establishes its symbiotic rapport with the host early in life. Early life perturbations of the developing gut microbiota can impact neurodevelopment and potentially lead to adverse mental health outcomes later in life. This review compares the p...
368 CitationsSource
#1Peter Verstraelen (University of Antwerp)H-Index: 6
#2Isabel Pintelon (University of Antwerp)H-Index: 19
Last. Jean-Pierre Timmermans (University of Antwerp)H-Index: 51
view all 6 authors...
Mental disorders, such as schizophrenia or Alzheimer’s disease, are associated with impaired synaptogenesis and/or synaptic communication. During development, neurons assemble into neuronal networks, the primary supracellular mediators of information processing. In addition to the orchestrated activation of genetic programs, spontaneous electrical activity and associated calcium signaling have been shown to be critically involved in the maturation of such neuronal networks. We established an in ...
18 CitationsSource
#1Kun-Long Hung (FJU: Fu Jen Catholic University)H-Index: 3
#2Su-Jane Wang (FJU: Fu Jen Catholic University)H-Index: 19
Last. Chia-Chuan Wang (FJU: Fu Jen Catholic University)H-Index: 17
view all 5 authors...
Although nerve injury-induced long-term postsynaptic changes have been investigated, less is known regarding the molecular mechanisms within presynaptic axonal terminals. We investigated the molecular changes in presynaptic nerve terminals underlying chronic pain-induced plastic changes in the medial prefrontal cortex (mPFC). After neuropathic pain was induced by spared nerve injury (SNI) in rats, we assessed the release of the excitatory neurotransmitter glutamate by using in vitro synaptosomal...
29 CitationsSource
#1Lieve Desbonnet (UCC: University College Cork)H-Index: 15
#2Gerard Clarke (UCC: University College Cork)H-Index: 47
Last. John F. Cryan (UCC: University College Cork)H-Index: 91
view all 5 authors...
The microbiota–gut–brain axis is an emerging concept in modern medicine informed by the ability of gut microbiota to alter brain and behaviour.1 Although some clinical studies have revealed altered gut microbiota composition in patients with neurodevelopmental disorders such as autism,2, 3 the specific contributions of microbiota in early life to the development and programming of the various facets of social behaviour has not been investigated.
312 CitationsSource
#1João P. Costa-Nunes (University of Lisbon)H-Index: 7
#2O. E. Zubareva (Academy of Medical Sciences, United Kingdom)H-Index: 4
Last. Tatyana Strekalova (University of Lisbon)H-Index: 22
view all 12 authors...
AbstractN-Methyl-d-aspartate receptor (NMDAR)-mediated neurotransmission in the hippocampus is implicated in cognitive and emotional disturbances during stress-related disorders. Here, using quantitative RT-PCR, we investigated the hippocampal expression of NR2A, NR2B and NR1 subunit mRNAs in a mouse stress paradigm that mimics clinically relevant conditions of simultaneously affected emotionality and hippocampus-dependent functions. A 2-week stress procedure, which comprised ethologically valid...
26 CitationsSource
#1Helene M. Savignac (University of Oxford)H-Index: 1
#2Giulia Corona (University of Reading)H-Index: 23
Last. Philip W.J. Burnet (University of Oxford)H-Index: 31
view all 7 authors...
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...
119 CitationsSource
Cited By28
#1John F. CryanH-Index: 91
Last. Timothy G. DinanH-Index: 88
view all 33 authors...
The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...
26 CitationsSource
#1Gwenola Le DreanH-Index: 1
Last. Catherine MichelH-Index: 17
view all 9 authors...
Oligosaccharides (OS) are commonly added to infant formulas, however, their physiological impact, particularly on adult health programming, is poorly described. In adult animals, OS modify microbiota and stimulate colonic fermentation and enteroendocrine cell (EEC) activity. Since neonatal changes in microbiota and/or EEC density could be long-lasting and EEC-derived peptides do regulate short-term food intake, we hypothesized that neonatal OS consumption could modulate early EECs, with possible...
1 CitationsSource
#1Siobhain M. O'Mahony (UCC: University College Cork)H-Index: 23
#2Karen-Anne McVey Neufeld (UCC: University College Cork)H-Index: 4
Last. John F. Cryan (UCC: University College Cork)H-Index: 91
view all 13 authors...
1 CitationsSource
#1Liliana Capitao (University of Oxford)H-Index: 6
#2Rita Baião (University of Oxford)H-Index: 1
Last. Philip W.J. Burnet (University of Oxford)H-Index: 31
view all 8 authors...
Based on the emerging interest in the effects of gut microbiota on cognition, this proof-of-concept study assessed how children aged 7 to 9 with low reading scores responded to the ingestion of a 3...
#1Kao Ac-C. (University of Oxford)H-Index: 1
#2K W Chan (University of Oxford)H-Index: 1
Last. Philip W.J. Burnet (University of Oxford)H-Index: 31
view all 5 authors...
Abstract The intestinal microbiome is emerging as a novel therapeutic target owing to the wide range of potential health benefits that could result by manipulating the microbiota composition through relatively simple interventions. Ingestion of the prebiotic Bimuno™ galacto-oligosaccharide (B-GOS®) is one such intervention that has been shown to attenuate olanzapine-induced weight gain and improve cognitive flexibility in rats, potentially through mechanisms involving acetate, the major short-ch...
1 CitationsSource
#1Luis G. Bermúdez-Humarán (Université Paris-Saclay)H-Index: 37
#2Eva SalinasH-Index: 1
Last. Oscar K. Bitzer-Quintero (Mexican Social Security Institute)H-Index: 8
view all 6 authors...
There is an important relationship between probiotics, psychobiotics and cognitive and behavioral processes, which include neurological, metabolic, hormonal and immunological signaling pathways; the alteration in these systems may cause alterations in behavior (mood) and cognitive level (learning and memory). Psychobiotics have been considered key elements in affective disorders and the immune system, in addition to their effect encompassing the regulation of neuroimmune regulation and control a...
5 CitationsSource
Last. Younes GhasemiH-Index: 27
view all 8 authors...
Prebiotics are a group of nutrients that are degraded by gut microbiota. Their relationship with human overall health has been an area of increasing interest in recent years. They can feed the intestinal microbiota, and their degradation products are short-chain fatty acids that are released into blood circulation, consequently, affecting not only the gastrointestinal tracts but also other distant organs. Fructo-oligosaccharides and galacto-oligosaccharides are the two important groups of prebio...
6 CitationsSource
#1Olivier Desmedt (UCL: Université catholique de Louvain)H-Index: 2
#2Valérie Broers (UCL: Université catholique de Louvain)H-Index: 2
Last. Olivier Luminet (UCL: Université catholique de Louvain)H-Index: 42
view all 6 authors...
2 CitationsSource
Gut microbiota has evolved along with their hosts and is an integral part of the human body. Microbiota acquired at birth develops in parallel as the host develops and maintains its temporal stability and diversity through adulthood until death. Recent developments in genome sequencing technologies, bioinformatics and culturomics have enabled researchers to explore the microbiota and in particular their functions at more detailed level than before. The accumulated evidences suggest that though a...
2 CitationsSource
#1Boushra DalileH-Index: 2
#2Kristin VerbekeH-Index: 50
Last. Bram VervlietH-Index: 29
view all 4 authors...