Neuro-Signals from Gut Microbiota: Perspectives for Brain Glioma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Gut Microbiota Influences the CNS: The Gut-Brain Axis
2.1. Gut Microbiota and Brain Disorders
2.2. Neuro-Signals from Gut Microbiota
2.3. Modulation of Neurotransmitter Levels by Gut Microbiota
3. Neurotransmitters beyond the Neuronal Function
3.1. Neurotransmitters Influence Physiological Cell Proliferation in Adult Brain
3.1.1. Dopamine
3.1.2. Serotonin
3.1.3. Norepinephrine
3.1.4. GABA
3.1.5. Glutamate
Neurotransmitters | Receptors | Effects | References |
---|---|---|---|
dopamine | n.d. | Increases NPC proliferation in SVZ | [115,116,117] |
D2-like | Promotes entry in S phase | [120] | |
D2-like | Decreases NPC proliferation | [118,119] | |
D1-like | Inhibits the entry in S phase | [121] | |
D3 | Inhibits the maturation of OPC | [122] | |
serotonin | n.d. | Depletion decreases proliferation in DG and SVZ | [123] |
5-HT1A | Blockade of receptors decreases proliferation in DG | [124] | |
n.d. | Increases NPC proliferation in DG | [125,126] | |
n.d. | Blocks OPC maturation | [127] | |
5-HT | Increases levels of trophic factors | [128,129,130,131] | |
norepinephrine | n.d. | Depletion decreases NPC proliferation but not differentiation in DG | [132] |
β3-AR | Increases proliferation of NPC in DG | [133] | |
a2-AR/β-AR | Balance in receptor activity regulates NPC activity in DG | [134] | |
n.d. | Reduces NPC proliferation in SVZ | [135] | |
gaba | extra synaptic GABA-A | Inhibits NPC proliferation in SVZ | [136] |
extra synaptic GABA-A | Regulates NPC production and migration | [137,138,139] | |
extra synaptic GABA-A | Maintains NPC quiescence in DG | [140] | |
synaptic GABA-A | Promotes NPC maturation in DG | [140] | |
glutamate | n.d. | Regulates adult neurogenesis | [114,142] |
mGluR5 | Promotes Neurogenesis in DG | [142,149] | |
NMDA | Promotes commitment and diferentiation in DG | [145,146,147,149] | |
NR2B | Increases dendritic arborization and contributes LTP induced neurogenesis | [148] |
3.2. Neurotransmitters Influence Glioma
3.2.1. Monoamines
3.2.2. Dopamine
3.2.3. Serotonin
3.2.4. Norepinephrine
3.2.5. GABA
3.2.6. Glutamate
Neurotransmitters | Receptors | Effects | References |
---|---|---|---|
dopamine | D2 | Regulates survival and cell proliferation | [155,156] |
D2 | Increases cancer stem cell-enriched spheroid proliferation | [158,159,160] | |
serotonin | 5-HT1, 5-HT2 | Increases cell proliferation | [172,173] |
5-HT2A | Increases cell proliferation and migration | [174] | |
n.d. | Induces cell differentiation | [175] | |
5-HT2A | Increases the release of neurotrophic factor GDNF | [176] | |
norepinephrine | β | Increases proliferation | [180] |
β2 | Inhibits proliferation | [181] | |
n.d. | Inhibits migration and invasion | [182] | |
gaba | GABA-A | Reduces cell proliferation sustaining cell quiescence | [186] |
glutamate | mGluR2/3 | Regulates cell growth | [193,194] |
GluR1/GluR4 | Increase cell proliferation and migration | [195] | |
AMPA | Promotes perivascular invasion | [196] | |
NMDA | Increases proliferation | [197] | |
n.d. | Drives tumor growth and invasion | [198,199,200,201] |
4. Do Gut Microbiota-Derived Neurotransmitters Affect Glioma Development?
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
GBM | Glioblastoma |
GF | Germ Free |
GABA | Gamma-aminobutyric acid |
CNS | Central nervous system |
5-HT | 5-hydroxytryptamine |
GI | Gastrointestinal |
SCFAs | Short-chain fatty acids |
BDNF | Brain derived neurotrophic factor |
ASD | Autism spectrum disorder |
PD | Parkinson’s disease |
AD | Alzheimer’s disease |
MS | Multiple sclerosis |
MIA | Maternal immune activation |
ASO | α-synuclein overexpressing |
Aβ | Amiloid–β |
EAE | Experimental autoimmune encephalomyelitis |
MCAO | Middle cerebral artery occlusion |
EECs | Enteroendocrine cells |
ANS | Autonomic nervous system |
ENS | Enteric nervous system |
LPS | Lipopolysaccharide |
GLP | Glucagon like peptide |
LBP | LPS binding protein |
BBB | Blood-brain barrier |
MCTs | Monocarboxylate transporters |
HPA | Hypothalamic-pituitary-adrenal |
CCK | Cholecystokinin |
NO | Nitric oxide |
BH4 | Tetrahydrobiopterin |
TH | Tyrosine hydroxylase |
5-HIAA | 5-hydroxyindoleacetic acid |
Kyn | Kynurine |
NMDA | N-methyl-D-aspartate |
AMPA | Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid |
SZ | Subventricular zone |
OPC | Oligodendrocyte progenitor cells |
DG | Dentate Gyrus |
β3AR | β3 adrenergic receptor |
GFAP | Glial fibrillary acidic protein |
NPCs | Neuronal precursor cells |
mGluR5 | metabotropic glutamate 5 receptor |
LTP | Long-term potentiation |
MAO-A | Monoamine oxidase A |
DRD-2 | Dopamine receptor D2 |
EGFR | Epidermal growth factor receptor |
NK | Natural killer |
SSRI | Selective serotonin reuptake inhibitor |
GDNF | Glial cell line-derived neurotrophic factor |
MMP | Matrix metalloproteinase |
GAD | Glutamate decarboxylase |
ABAT | 4-aminobutyrate aminotransferase |
NLGN3 | Neuroligin-3 |
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Neurotransmitters | Microbes | Effects | References |
---|---|---|---|
dopamine | Enterococcus faecium and Lactobacillus rhamnosus | Increased levels in healthy mouse brain | [77] |
n.d. | Increased turnover rate in the brain striatum of GF mice | [12] | |
Lactobacillus plantarum | Increased levels in the brain striatum of GF mice | [79] | |
Enterococcus faecalis, Enterococcus faecium | Increased levels in brain, blood, and feces of the pseudo GF mice | [78] | |
Enterococcus faecalis, Enterococcus faecium, Proteus mirabilis, Lactobacillus acidophilus | Increase level in vitro | [78] | |
Clostridium species | Restored levels in the lumen of GF mice | [73] | |
serotonin | Lactobacillus plantarum | Increased levels in the brain striatum of GF mice | [79] |
n.d. | Increased turnover rate in the brain striatum of GF mice | [12] | |
n.d. | Increased levels in hippocampus of male GF mice | [80] | |
norepinephrine | Clostridium species | Restore levels in the lumen of GF mice | [73] |
n.d | Increased turnover rate in the brain striatum of GF mice | [12] | |
gaba | n.d. | Reduced levels in gut lumen of GF mice | [81] |
Lactobacillus rhamnosus | Modulated GABA receptor mRNA expression in healthy mice brains | [70] | |
Enterococcus faecium and Lactobacillus rhamnosus | Increased levels in healthy mice brains | [77] | |
Lactobacillus rhamnosus | Increased brain levels in healthy mice | [82] | |
glutamate | Lactobacillus rhamnosus | Increased brain levels in healthy mice | [82,83] |
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D’Alessandro, G.; Lauro, C.; Quaglio, D.; Ghirga, F.; Botta, B.; Trettel, F.; Limatola, C. Neuro-Signals from Gut Microbiota: Perspectives for Brain Glioma. Cancers 2021, 13, 2810. https://doi.org/10.3390/cancers13112810
D’Alessandro G, Lauro C, Quaglio D, Ghirga F, Botta B, Trettel F, Limatola C. Neuro-Signals from Gut Microbiota: Perspectives for Brain Glioma. Cancers. 2021; 13(11):2810. https://doi.org/10.3390/cancers13112810
Chicago/Turabian StyleD’Alessandro, Giuseppina, Clotilde Lauro, Deborah Quaglio, Francesca Ghirga, Bruno Botta, Flavia Trettel, and Cristina Limatola. 2021. "Neuro-Signals from Gut Microbiota: Perspectives for Brain Glioma" Cancers 13, no. 11: 2810. https://doi.org/10.3390/cancers13112810