scholarly journals Fetal Exposure to Acetochlor Impaired Cognitive Function in Rats via Abnormal Gut Microbiome and Metabolic Disorders

2021 ◽  
Author(s):  
Wei Wei ◽  
Huanyu Wu ◽  
Wenbo Gu ◽  
Jiaxu Xu ◽  
Cong Hu ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Gut Microbiome ◽  
Long Term Potentiation ◽  
Fecal Microbiota ◽  
Intestinal Microbiome ◽  
Abnormal Behavior ◽  
Current Evidence ◽  
Fetal Exposure ◽  
Cognitive Behaviors ◽  
Impaired Cognitive Function

Abstract Background: Current evidence has shown that acetochlor has adverse effects on health, which has been widely used in agricultural production, while the evidence on the effects of fetal acetochlor exposure on nervous system is quite limited. The fetus period is the most sensitive window period in the whole lifetime to external stimuli. Therefore, we established a rat model fetal exposed to acetochlor. Results: Impaired cognitive function, abnormal gut microbiome and significant changes in the hippocampus and colon could be observed in the acetochlor-exposed group. We also observed remarkable impairment in the hippocampal cells in the histomorphology observation. Fecal microbiota transplantion(FMT) was performed to elucidate whether the gut microbiome mediated the acetochlor-induced abnormal behavior. Then the proteomics analysis and metabonomics analysis in the hippocampus indicated that differential expression proteins were mainly enriched in amino acid neurotransmitter-related pathways, long-term potentiation, and synaptic-related pathways and differential metabolite were mainly enriched in mutiple neurotransmitter-related pathways. Then we observed remarkable changes in the Camk2b/Erk1/2/NF-κB pathway and Prkaca/p-CREB1/BDNF pathway in the FMT group, which may cause abnormal cognitive behaviors. Conclusions: Our results demonstrate that fetal exposure to acetochlor could induce abnormal behaviors in rats via disrupting the intestinal microbiome.

scholarly journals Fetal exposure to dichloroacetic acid and impaired cognitive function in the adulthood

2020 ◽  
Vol 10 (10) ◽  
Author(s):  
Yue Wang ◽  
Wenbo Jiang ◽  
Qiuying Dong ◽  
Yue Zhao ◽  
Yingying Chen ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Dichloroacetic Acid ◽  
Fetal Exposure ◽  
Impaired Cognitive Function

Protective Effects of DAla2-GIP-GLU-PAL against Cognitive Deficits and Amyloid Deposition in APP/PS1 AD Mice Associated with Reduction of Neuroinflammation

2020 ◽  
Author(s):  
Jinshun Qi ◽  
Li Yuan ◽  
Jun Zhang ◽  
Christian Holscher ◽  
Jun-Ting Yang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Object Recognition ◽  
Cognitive Function ◽  
Late Phase ◽  
Amyloid Β ◽  
Long Term Potentiation ◽  
Cognitive Behaviors ◽  
The Brain

Abstract Background Alzhermer’s disease (AD) is a neurodegenerative disease characterized by progressive decline in cognitive function and high-density deposition of amyloid-β (Aβ) plaques in the brain. Type 2 diabetes mellitus (T2DM) is an important risk factor for AD. Glucose-dependent insulinotropic polypeptide (GIP) has been identified to be effective in T2DM treatment and neuroprotection. The present study further investigated the neuroprotective effects of a novel long lasting GIP analogue DAla2GIP-Glu-PAL in 9-month-old APP swe /PS1 dE9 (APP/PS1) AD mice. Methods Multiple behavioral tests including new object recognition, Y maze and Morris water maze were performed to examine the cognitive function of mice. In vivo hippocampal late-phase long-term potentiation (L-LTP) was recorded to reflect synaptic plasticity. Immunohistochemistry and immunofluorescence were used to examine the Aβ plaques and neuroinflammation in the brain. The expression levels of cAMP, S99 p-PKA, S133 p-CREB, S468 NF-κBp65 and IL-1β were detected by western blotting or ELISA. Results DAla2GIP-Glu-PAL effectively improved cognitive behaviors and synaptic plasticity of APP/PS1 mice, with increased new object recognition, spontaneous alternation and target quadrant swimming time, as well as enhanced in vivo hippocampal L-LTP. DAla2GIP-Glu-PAL significantly reduced Aβ deposition and inhibited astrocyte proliferation, IL-1β secretion and NF-κB activation. Besides, . DAla2GIP-Glu-PAL also up-regulated cAMP/PKA/CREB signal transduction in the hippocampus of APP/PS1 mice. Conclusion DAla2GIP-Glu-PAL improves cognitive behaviors, long-term synaptic plasticity and pathological damages in APP/PS1 mice, which are associated with the reduction of neuroinflammation and the up-regulation of cAMP/PKA/CREB signaling in the hippocampus. This study suggests a potential benefit of DAla2GIP-Glu-PAL in the treatment of AD.

scholarly journals Sulpiride Serves, a Substrate for the Gut Microbiome

Dose-Response ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 155932582098794
Author(s):  
Imran Mukhtar ◽  
Haseeb Anwar ◽  
Osman Asghar Mirza ◽  
Qasim Ali ◽  
Muhammad Umar Ijaz ◽  
...  
Keyword(s):  
Oral Administration ◽  
Gut Microbiome ◽  
Drug Target ◽  
Membrane Transporters ◽  
Intestinal Microbiome ◽  
Albino Rats ◽  
Body Organ ◽  
Total Absorbance ◽  
Research World

In the contemporary research world, the intestinal microbiome is now envisioned as a new body organ. Recently, the gut microbiome represents a new drug target in the gut, since various orthologues of intestinal drug transporters are also found present in the microbiome that lines the small intestine of the host. Owing to this, absorbance of sulpiride by the gut microbiome in an in vivo albino rats model was assessed after the oral administration with a single dose of 20mg/kg b.w. The rats were subsequently sacrificed at 2, 3, 4, 5 and 6 hours post oral administration to collect the gut microbial mass pellet. The drug absorbance by the gut microbiome was determined by pursuing the microbial lysate through RP-HPLC-UV. Total absorbance of sulpiride by the whole gut microbiome and drug absorbance per milligram of microbial pellet were found significantly higher at 4 hours post-administration as compared to all other groups. These results affirm the hypothesis that the structural homology between membrane transporters of the gut microbiome and intestinal epithelium of the host might play an important role in drug absorbance by gut microbes in an in vivo condition.

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