title: Neuronal plasticity in the cingulate cortex of rats following esophageal acid exposure in early life.
abstract: OBJECTIVE
  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.
authors: Division of Gastroenterology & Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors: Banani
authors: B
authors: Banerjee
authors: Bidyut K
authors: BK
authors: Medda
authors: Jamie
authors: J
authors: Schmidt
authors: Ivan M
authors: IM
authors: Lang
authors: Jyoti N
authors: JN
authors: Sengupta
authors: Reza
authors: R
authors: Shaker
references: Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18769-74
references: 17124177
references: Eur J Neurosci. 2008 Feb;27(3):644-53
references: 18279317
references: Pain. 2006 Dec 5;125(3):278-285
references: 17011707
references: Gastroenterology. 2005 Mar;128(3):610-9
references: 15765397
references: Gastroenterology. 2000 Nov;119(5):1276-85
references: 11054385
references: Trends Neurosci. 1995 Feb;18(2):54-6
references: 7537406
references: Gastroenterology. 2009 May;136(5):1732-40.e3
references: 19208366
references: Gastroenterology. 2004 Mar;126(3):683-92
references: 14988822
references: Mol Pharmacol. 2001 May;59(5):960-4
references: 11306676
references: Neuroscience. 2000;98(2):201-6
references: 10854750
references: Neuropharmacology. 2007 Sep;53(3):362-8
references: 17644144
references: J Neurosci. 2006 Aug 30;26(35):8923-30
references: 16943548
references: Brain Res. 2002 Aug 30;947(2):252-9
references: 12176168
references: Behav Brain Res. 2005 Nov 7;164(2):231-8
references: 16125259
references: Neurochem Res. 1993 Jan;18(1):65-77
references: 8385278
references: Gastroenterology. 1998 Dec;115(6):1353-62
references: 9834262
references: Science. 1999 Sep 17;285(5435):1870-4
references: 10489359
references: J Pain. 2006 Jul;7(7):469-79
references: 16814686
references: Nat Rev Neurosci. 2004 Oct;5(10):771-81
references: 15378037
references: J Biol Chem. 1999 Sep 10;274(37):26199-208
references: 10473573
references: J Biol Chem. 2000 Aug 4;275(31):23798-806
references: 10764765
references: Neuroscience. 2009 Jan 12;158(1):324-33
references: 18773944
references: J Neurosci. 2002 May 15;22(10):4196-204
references: 12019337
references: Brain Res. 2007 Jul 16;1158:39-49
references: 17559813
references: Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G307-16
references: 11804852
references: Pain. 2010 Aug;150(2):257-267
references: 20471751
references: Am J Gastroenterol. 2008 Mar;103(3):765-74; quiz 775
references: 18177446
references: J Neurosci. 2008 Mar 19;28(12):3060-70
references: 18354009
references: Trends Neurosci. 2000 Feb;23(2):75-80
references: 10652548
references: Am J Physiol Gastrointest Liver Physiol. 2008 Mar;294(3):G787-94
references: 18187518
references: Annu Rev Physiol. 2000;62:755-78
references: 10845110
references: J Comp Neurol. 2002 Jun 17;448(1):102-10
references: 12012376
references: Neuroreport. 2001 Oct 29;12(15):3251-5
references: 11711866
references: Annu Rev Biochem. 1992;61:559-601
references: 1323238
references: Brain Res Mol Brain Res. 2005 Dec 7;142(1):65-79
references: 16257472
references: Curr Top Cell Regul. 1990;31:181-221
references: 2173993
references: J Physiol. 2009 Jun 15;587(Pt 12):2927-35
references: 19403624
references: Anesth Analg. 2003 Oct;97(4):1108-1116
references: 14500166
references: Histochem Cell Biol. 2009 Dec;132(6):585-97
references: 19784665
references: Neurochem Int. 1996 Apr;28(4):343-58
references: 8740440
references: Nat Neurosci. 1999 Apr;2(4):331-8
references: 10204539
references: J Physiol. 2006 May 1;572(Pt 3):775-87
references: 16513666
references: J Neurochem. 1993 Jul;61(1):100-9
references: 7685812
references: Biochem Biophys Res Commun. 1991 Dec 31;181(3):968-75
references: 1662507
references: Gastroenterology. 2008 Feb;134(2):535-43
references: 18242219
references: Pharmacol Ther. 2006 Dec;112(3):810-32
references: 16904750
references: Neuron. 2002 Apr 11;34(2):255-64
references: 11970867
references: Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):14163-8
references: 18779583
references: Am J Physiol Gastrointest Liver Physiol. 2008 Apr;294(4):G918-27
references: 18258793