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Neuronal plasticity in the cingulate cortex of rats following esophageal acid exposure in early life. Gastroenterology 2011 Aug;141(2):544-52

Date

05/28/2011

Pubmed ID

21616075

Pubmed Central ID

PMC3152593

DOI

10.1053/j.gastro.2011.04.044

Abstract

BACKGROUND & AIMS: The cingulate cortex has been reported to be involved in processing pain of esophageal origin. However, little is known about molecular changes and cortical activation that arise from early-life esophageal acid reflux. Excitatory neurotransmission via activation of the N-methyl-d-aspartate (NMDA) receptor and its interaction with postsynaptic density protein 95 (PSD-95) at the synapse appear to mediate neuronal development and plasticity. We investigated the effect of early-life esophageal acid exposure on NMDA receptor subunits and PSD-95 expression in the developing cingulate cortex.

METHODS: We assessed NMDA receptor subunits and PSD-95 protein expression in rostral cingulate cortex (rCC) tissues of rats exposed to esophageal acid or saline (control), either during postnatal day (P) 7 to 14 and/or acutely at adult stage (P60) using immunoblot and immunoprecipitation analyses.

RESULTS: Compared with controls, acid exposure from P7 to P14 significantly increased expression of NR1, NR2A, and PSD-95, measured 6 weeks after exposure. However, acute exposure at P60 caused a transient increase in expression of NMDA receptor subunits. These molecular changes were more robust in animals exposed to acid neonatally and rechallenged, acutely, at P60. Esophageal acid exposure induced calcium calmodulin kinase II-mediated phosphorylation of the subunit NR2B at Ser1303.

CONCLUSIONS: Esophageal acid exposure during early stages of life has long-term effects as a result of phosphorylation of the NMDA receptor and overexpression in the rCC. This molecular alteration in the rCC might mediate sensitization of patients with acid-induced esophageal disorders.

Author List

Banerjee B, Medda BK, Schmidt J, Lang IM, Sengupta JN, Shaker R

Authors

Banani Banerjee PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Ivan M. Lang DVM, PhD 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 Assoc Provost, Sr Assoc Dean, Ctr Dir, Chief, Prof in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Disks Large Homolog 4 Protein
Esophagus
Gyrus Cinguli
Hydrochloric Acid
Intracellular Signaling Peptides and Proteins
Male
Membrane Proteins
Neuronal Plasticity
Phosphorylation
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate
Synaptic Membranes
Time Factors
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75