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Prolonged esophageal acid exposures induce synaptic downscaling of cortical membrane AMPA receptor subunits in rats. Neurogastroenterol Motil 2016 Sep;28(9):1356-69 PMID: 27271201 PMCID: PMC5063079

Abstract

BACKGROUND: We recently reported the involvement of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor subunit upregulation and phosphorylation in the rostral cingulate cortex (rCC) as the underlying mechanism of acute esophageal acid-induced cortical sensitization. Based on these findings, we proposed to investigate whether prolonged esophageal acid exposures in rats exhibit homeostatic synaptic scaling through downregulation of AMPA receptor expression in rCC neurons. We intended to study further whether this compensatory mechanism is impaired when rats are pre-exposed to repeated esophageal acid exposures neonatally during neuronal development.

METHODS: Two different esophageal acid exposure protocols in rats were used. Since AMPA receptor trafficking and channel conductance depend on CaMKIIα-mediated phosphorylation of AMPA receptor subunits, we examined the effect of esophageal acid on CaMKIIα activation and AMPA receptor expression in synaptoneurosomes and membrane preparations from rCCs.

KEY RESULTS: In cortical membrane preparations, GluA1 and pGluA1Ser(831) expression were significantly downregulated following prolonged acid exposures in adult rats; this was accompanied by the significant downregulation of cortical membrane pCaMKIIα expression. No change in GluA1 and pGluA1Ser(831) expression was observed in rCC membrane preparations in rats pre-exposed to acid neonatally followed by adult rechallenge.

CONCLUSIONS & INFERENCES: This study along with our previous findings suggests that synaptic AMPA receptor subunits expression and phosphorylation may be involved bidirectionally in both esophageal acid-induced neuronal sensitization and acid-dependent homeostatic plasticity in cortical neurons. The impairment of homeostatic compensatory mechanism as observed following early-in-life acid exposure could be the underlying mechanism of heightening cortical sensitization and esophageal hypersensitivity in patients with gastroesophageal reflux disease.

Author List

Banerjee B, Medda BK, Zhang J, Tuchscherer V, Babygirija R, Kannampalli P, Sengupta JN, Shaker R

Authors

Banani Banerjee PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Bidyut K. Medda PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Jyoti N. Sengupta PhD Professor in the Medicine department at Medical College of Wisconsin
Reza Shaker MD Sr Associate Dean, Ctr Director, Chief, Professor in the Medicine department at Medical College of Wisconsin



View this publication's entry at the Pubmed website PMID: 27271201
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