MiR‐33‐5p‐opioidergic Signaling Regulates Cognitive Impairment Induced by Bile Duct Ligation in Rats: Ameliorative Role of Naloxone

TL;DR

This study shows that bile duct ligation in rats causes cognitive issues through miR-33-5p-opioid signaling, and these issues can be improved with naloxone.

Contribution

The study identifies miR-33-5p-opioid signaling as a novel pathway in cognitive impairment from bile duct ligation and suggests naloxone as a potential treatment.

Findings

BDL caused elevated liver function tests and cognitive impairment in rats.

Naloxone improved memory and plasticity and reduced miR-33-5p overexpression in the hippocampus.

Histopathological changes in the liver and hippocampus were reduced by naloxone.

Abstract

The present study investigated the involvement of miR‐33‐5p‐opioidergic signaling in the regulation of cognitive impairment induced by bile duct ligation (BDL) in rats, with an emphasis on the ameliorative role of naloxone.

Among the four groups of Wistar rats (control, sham, BDL, and BDL + Naloxone [Nalx]), the common bile duct was occluded only in the BDL groups. Fourteen days after BDL induction and following completion of the analysis of the liver function tests of alkaline phosphatase, alanine aminotransferase, aspartate transaminase, direct bilirubin, total bilirubin, gamma‐glutamyl transpeptidase (GGT), and lactate dehydrogenase, the cognitive tests and electrophysiological field potential responses were recorded. Then, the hippocampus was assessed for the expression level of miR‐33‐5p using PCR. Ultimately, a histopathological study of the liver and hippocampus was carried out.

The findings revealed that except for GGT (p = 0.1935), all liver function tests were elevated (P = 0.0001) following BDL. The impaired inhibitory avoidance memory (P < 0.0001) and plasticity (P < 0.0001) and the hippocampal overexpression of miR‐33‐5p following BDL (P <0.0001) were ameliorated by Nalx. In a qualitative histopathological study of the liver and hippocampus, Nalx attenuated the BDL‐induced changes.

It is concluded that the BDL‐mediated dysfunction has a molecular, electrophysiological, and histopathological basis and might be regulated via miR‐33‐5p and opioidergic signaling. The study emphasizes the potential ameliorative role of Nalx on biliary and nervous system pathologies.

Bile‐duct ligation (BDL)‐induced memory impairment has a molecular, electrophysiological and histopathological basis and might be regulated by miR‐33‐opioid signaling. The modulation of miR in the brain may be a novel therapeutic approach for relieving neuropathological problems in cholestatic cases, and individuals with cholestasis may benefit from new therapeutic approaches that focus on this brain circuit in terms of cognitive and synaptic plasticity.

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