Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice.
10.1016/j.apsb.2019.07.001
- Author:
Xueqin YANG
1
;
Dongke YU
2
;
Li XUE
1
;
Hui LI
1
;
Junrong DU
1
Author Information
1. Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
2. Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, 610072, China.
- Publication Type:Journal Article
- Keywords:
8-OHdG, 8-hydroxydesoxyguanosine;
AAMI, age-associated memory impairment;
AD, Alzheimer's disease;
BBB, blood–brain barrier;
CFU, colony-forming units;
Cognitive decline;
ELISA, enzyme-linked immunosorbent assay;
F/B, Firmicutes/Bacteroidetes;
GFAP, glial fibrillary acidic protein;
HE, hematoxylin and eosin;
IHC, immunohistochemistry;
IL-6, interleukin-6;
Iba-1, ionized calcium binding adaptor molecule-1;
LPS, lipopolysaccharide;
MCI, mild cognitive impairment;
Microbiota–gut–brain axis;
NF-κB;
NF-κB, nuclear factor-κB;
NMDS, non-metric multidimensional scaling;
OTU, operational taxonomic unit;
PAMP, pathogen-associated molecular pattern;
Probiotics;
RIG-I;
RIG-I, retinoic-acid-inducible gene-I;
SAMP8 mice;
SAMP8, senescence-accelerated mouse prone 8;
SYN, synaptophysin;
TEM, transmission electron microscopy;
TLR4;
TLR4, toll-like receptor 4;
TNF-α, tumor necrosis factor-α;
VE-cadherin, vascular endothelial-cadherin;
ZO-1, zona occluden-1
- From:
Acta Pharmaceutica Sinica B
2020;10(3):475-487
- CountryChina
- Language:English
-
Abstract:
ProBiotic-4 is a probiotic preparation composed of , , , and . This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits, and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8 (SAMP8) mice. ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks. We observed that ProBiotic-4 significantly improved the memory deficits, cerebral neuronal and synaptic injuries, glial activation, and microbiota composition in the feces and brains of aged SAMP8 mice. ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood-brain barrier, decreased interleukin-6 and tumor necrosis factor- at both mRNA and protein levels, reduced plasma and cerebral lipopolysaccharide (LPS) concentration, toll-like receptor 4 (TLR4) expression, and nuclear factor-B (NF-B) nuclear translocation in the brain. In addition, not only did ProBiotic-4 significantly decreased the levels of -H2AX, 8-hydroxydesoxyguanosine, and retinoic-acid-inducible gene-I (RIG-I), it also abrogated RIG-I multimerization in the brain. These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiota-gut-brain axis and cognitive function in aging, and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NF-B signaling pathway and inflammatory responses.
