Sodium P-aminosalicylic acid inhibits sub-chronic manganese-induced neuroinflammation in rats by modulating MAPK and COX-2

Shao Jun Li, Wen Xia Qin, Dong Jie Peng, Zong Xiang Yuan, Sheng Nan He, Yi Ni Luo, Michael Aschner, Yue Ming Jiang, Dian Yin Liang, Bing Yan Xie, Fang Xu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Excessive manganese (Mn) accumulation in the brain may induce an extrapyramidal disorder known as manganism. Inflammatory processes play a critical role in neurodegenerative diseases. Therapeutically, non-steroidal anti-inflammatory drugs or analogous anti-inflammatory therapies have neuroprotective effects. As a non-steroidal anti-inflammatory drug, p-aminosalicylic acid (PAS) has anti-inflammatory effects, which are mediated by decreased prostaglandins E2 (PGE2) levels. The aim of the current study was to investigate whether PAS-Na treatment prevents Mn-induced behavioral changes and neuroinflammation in vivo. Male Sprague-Dawley rats were intraperitoneally (i.p.) injected with MnCl2·4H2O (15mg/kg) for 12 weeks, followed by 6 weeks PAS-Na treatment. Sub-chronic Mn exposure increased Mn levels in the whole blood, cortex, hippocampus and thalamus, and induced learning and memory deficits, concomitant with astrocytes activation in the cortex, hippocampus and thalamus. Moreover inflammatory cytokine levels in serum and brain of Mn-treated group were increased, including IL-1β, IL-6, TNF-αand PGE2, especially in the hippocampus and thalamus. Furthermore, sub-chronic Mn exposure also increased inflammatory cytokines and COX-2 in transcription levels concomitant with increased MAPK signaling and COX-2 in the same selected brain regions. PAS-Na treatment at the highest doses also decreased Mn levels in the whole blood and selected brain tissues, and reversed the Mn-induced learning and memory deficits. PAS-Na inhibited astrocyte activation as well as the Mn-induced increase in inflammatory cytokine levels, reducing p38, ERK MAPK pathway and COX-2 activity. In contrast PAS-Na had no effects on the JNK MAPK pathway. These data establish the efficacy of PAS-Na not only as a chelating agent to mobilize whole blood Mn, but also as an anti-inflammatory agent.

Original languageEnglish (US)
JournalNeuroToxicology
DOIs
StateAccepted/In press - 2017

Fingerprint

Aminosalicylic Acid
Manganese
Rats
Sodium
Anti-Inflammatory Agents
Brain
Thalamus
Hippocampus
Blood
MAP Kinase Signaling System
Memory Disorders
Cytokines
Dinoprostone
Astrocytes
Chemical activation
Learning
Basal Ganglia Diseases
Neurodegenerative diseases
Data storage equipment
Neuroprotective Agents

Keywords

  • Inflammatory process
  • Learning and memory deficits
  • Manganese
  • MAPK pathway
  • Sodium para-aminosalicylate

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Sodium P-aminosalicylic acid inhibits sub-chronic manganese-induced neuroinflammation in rats by modulating MAPK and COX-2. / Li, Shao Jun; Qin, Wen Xia; Peng, Dong Jie; Yuan, Zong Xiang; He, Sheng Nan; Luo, Yi Ni; Aschner, Michael; Jiang, Yue Ming; Liang, Dian Yin; Xie, Bing Yan; Xu, Fang.

In: NeuroToxicology, 2017.

Research output: Contribution to journalArticle

Li, Shao Jun ; Qin, Wen Xia ; Peng, Dong Jie ; Yuan, Zong Xiang ; He, Sheng Nan ; Luo, Yi Ni ; Aschner, Michael ; Jiang, Yue Ming ; Liang, Dian Yin ; Xie, Bing Yan ; Xu, Fang. / Sodium P-aminosalicylic acid inhibits sub-chronic manganese-induced neuroinflammation in rats by modulating MAPK and COX-2. In: NeuroToxicology. 2017.
@article{f091ed3e4fba41afae7815eb74bdde86,
title = "Sodium P-aminosalicylic acid inhibits sub-chronic manganese-induced neuroinflammation in rats by modulating MAPK and COX-2",
abstract = "Excessive manganese (Mn) accumulation in the brain may induce an extrapyramidal disorder known as manganism. Inflammatory processes play a critical role in neurodegenerative diseases. Therapeutically, non-steroidal anti-inflammatory drugs or analogous anti-inflammatory therapies have neuroprotective effects. As a non-steroidal anti-inflammatory drug, p-aminosalicylic acid (PAS) has anti-inflammatory effects, which are mediated by decreased prostaglandins E2 (PGE2) levels. The aim of the current study was to investigate whether PAS-Na treatment prevents Mn-induced behavioral changes and neuroinflammation in vivo. Male Sprague-Dawley rats were intraperitoneally (i.p.) injected with MnCl2·4H2O (15mg/kg) for 12 weeks, followed by 6 weeks PAS-Na treatment. Sub-chronic Mn exposure increased Mn levels in the whole blood, cortex, hippocampus and thalamus, and induced learning and memory deficits, concomitant with astrocytes activation in the cortex, hippocampus and thalamus. Moreover inflammatory cytokine levels in serum and brain of Mn-treated group were increased, including IL-1β, IL-6, TNF-αand PGE2, especially in the hippocampus and thalamus. Furthermore, sub-chronic Mn exposure also increased inflammatory cytokines and COX-2 in transcription levels concomitant with increased MAPK signaling and COX-2 in the same selected brain regions. PAS-Na treatment at the highest doses also decreased Mn levels in the whole blood and selected brain tissues, and reversed the Mn-induced learning and memory deficits. PAS-Na inhibited astrocyte activation as well as the Mn-induced increase in inflammatory cytokine levels, reducing p38, ERK MAPK pathway and COX-2 activity. In contrast PAS-Na had no effects on the JNK MAPK pathway. These data establish the efficacy of PAS-Na not only as a chelating agent to mobilize whole blood Mn, but also as an anti-inflammatory agent.",
keywords = "Inflammatory process, Learning and memory deficits, Manganese, MAPK pathway, Sodium para-aminosalicylate",
author = "Li, {Shao Jun} and Qin, {Wen Xia} and Peng, {Dong Jie} and Yuan, {Zong Xiang} and He, {Sheng Nan} and Luo, {Yi Ni} and Michael Aschner and Jiang, {Yue Ming} and Liang, {Dian Yin} and Xie, {Bing Yan} and Fang Xu",
year = "2017",
doi = "10.1016/j.neuro.2017.06.012",
language = "English (US)",
journal = "NeuroToxicology",
issn = "0161-813X",
publisher = "Elsevier",

}

TY - JOUR

T1 - Sodium P-aminosalicylic acid inhibits sub-chronic manganese-induced neuroinflammation in rats by modulating MAPK and COX-2

AU - Li, Shao Jun

AU - Qin, Wen Xia

AU - Peng, Dong Jie

AU - Yuan, Zong Xiang

AU - He, Sheng Nan

AU - Luo, Yi Ni

AU - Aschner, Michael

AU - Jiang, Yue Ming

AU - Liang, Dian Yin

AU - Xie, Bing Yan

AU - Xu, Fang

PY - 2017

Y1 - 2017

N2 - Excessive manganese (Mn) accumulation in the brain may induce an extrapyramidal disorder known as manganism. Inflammatory processes play a critical role in neurodegenerative diseases. Therapeutically, non-steroidal anti-inflammatory drugs or analogous anti-inflammatory therapies have neuroprotective effects. As a non-steroidal anti-inflammatory drug, p-aminosalicylic acid (PAS) has anti-inflammatory effects, which are mediated by decreased prostaglandins E2 (PGE2) levels. The aim of the current study was to investigate whether PAS-Na treatment prevents Mn-induced behavioral changes and neuroinflammation in vivo. Male Sprague-Dawley rats were intraperitoneally (i.p.) injected with MnCl2·4H2O (15mg/kg) for 12 weeks, followed by 6 weeks PAS-Na treatment. Sub-chronic Mn exposure increased Mn levels in the whole blood, cortex, hippocampus and thalamus, and induced learning and memory deficits, concomitant with astrocytes activation in the cortex, hippocampus and thalamus. Moreover inflammatory cytokine levels in serum and brain of Mn-treated group were increased, including IL-1β, IL-6, TNF-αand PGE2, especially in the hippocampus and thalamus. Furthermore, sub-chronic Mn exposure also increased inflammatory cytokines and COX-2 in transcription levels concomitant with increased MAPK signaling and COX-2 in the same selected brain regions. PAS-Na treatment at the highest doses also decreased Mn levels in the whole blood and selected brain tissues, and reversed the Mn-induced learning and memory deficits. PAS-Na inhibited astrocyte activation as well as the Mn-induced increase in inflammatory cytokine levels, reducing p38, ERK MAPK pathway and COX-2 activity. In contrast PAS-Na had no effects on the JNK MAPK pathway. These data establish the efficacy of PAS-Na not only as a chelating agent to mobilize whole blood Mn, but also as an anti-inflammatory agent.

AB - Excessive manganese (Mn) accumulation in the brain may induce an extrapyramidal disorder known as manganism. Inflammatory processes play a critical role in neurodegenerative diseases. Therapeutically, non-steroidal anti-inflammatory drugs or analogous anti-inflammatory therapies have neuroprotective effects. As a non-steroidal anti-inflammatory drug, p-aminosalicylic acid (PAS) has anti-inflammatory effects, which are mediated by decreased prostaglandins E2 (PGE2) levels. The aim of the current study was to investigate whether PAS-Na treatment prevents Mn-induced behavioral changes and neuroinflammation in vivo. Male Sprague-Dawley rats were intraperitoneally (i.p.) injected with MnCl2·4H2O (15mg/kg) for 12 weeks, followed by 6 weeks PAS-Na treatment. Sub-chronic Mn exposure increased Mn levels in the whole blood, cortex, hippocampus and thalamus, and induced learning and memory deficits, concomitant with astrocytes activation in the cortex, hippocampus and thalamus. Moreover inflammatory cytokine levels in serum and brain of Mn-treated group were increased, including IL-1β, IL-6, TNF-αand PGE2, especially in the hippocampus and thalamus. Furthermore, sub-chronic Mn exposure also increased inflammatory cytokines and COX-2 in transcription levels concomitant with increased MAPK signaling and COX-2 in the same selected brain regions. PAS-Na treatment at the highest doses also decreased Mn levels in the whole blood and selected brain tissues, and reversed the Mn-induced learning and memory deficits. PAS-Na inhibited astrocyte activation as well as the Mn-induced increase in inflammatory cytokine levels, reducing p38, ERK MAPK pathway and COX-2 activity. In contrast PAS-Na had no effects on the JNK MAPK pathway. These data establish the efficacy of PAS-Na not only as a chelating agent to mobilize whole blood Mn, but also as an anti-inflammatory agent.

KW - Inflammatory process

KW - Learning and memory deficits

KW - Manganese

KW - MAPK pathway

KW - Sodium para-aminosalicylate

UR - http://www.scopus.com/inward/record.url?scp=85023185370&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85023185370&partnerID=8YFLogxK

U2 - 10.1016/j.neuro.2017.06.012

DO - 10.1016/j.neuro.2017.06.012

M3 - Article

JO - NeuroToxicology

JF - NeuroToxicology

SN - 0161-813X

ER -