Brain effects of chronic IBD in areas abnormal in autism and treatment by single neuropeptides secretin and oxytocin

J Mol Neurosci. 2005;25(3):259-74. doi: 10.1385/JMN:25:3:259.

Abstract

Recent research points to the connection between behavioral and gut disorders. Early adverse events are associated with inflammatory bowel disease (IBD). In animal models, maternal deprivation and social isolation predispose to gastric erosion and brain pathology. This study examined (1) brain effects of chronic gastrointestinal inflammation in a rat model of acquired IBD and (2) whether such changes are resolved by individual secretin (S) or oxytocin (OT) peptide treatment. Neurological manifestations of IBD were mapped by c-fos gene expression in male Sprague-Dawley rats (n = 10) with trinitrobenzene sulfonic acid (TNBS)-induced IBD vs controls (n = 11). IBD was characterized by moderate/severe infiltration of inflammatory cells 10 d after TNBS infusion. Age-matched pairs were processed for immunocytochemical detection of Fos, expressed when neurons are stimulated. S or OT (100 mg/250 mL saline) or equivolume saline was administered iv by Alzet pump for 20 d after disease onset. Degree of resolution of colitis-induced brain activation was assessed by c-fos expression, and mean numbers of Fos-immunoreactive nuclei for each group were compared using Independent Samples T-test. Chronic IBD activated periventricular gray, hypothalamic/visceral thalamic stress axes and cortical domains, and septal/preoptic/amygdala, brain areas abnormal in autism. Single peptide treatment with S or OT did not alter the effects of inflammation on the brain. Brain areas concomitantly activated by visceral inflammation are those often abnormal in autism, suggesting that IBD could be a model for testing treatments of autism. Other single and combined peptide treatments of IBD should be tested. The clinical implications for treating autism, IBD, and concomitant sickness behaviors with peptide therapy, with or without maternal nurturing as a natural equivalent, are presented.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amygdala / drug effects
  • Amygdala / physiopathology
  • Animals
  • Autistic Disorder / complications
  • Autistic Disorder / drug therapy*
  • Autistic Disorder / physiopathology*
  • Chronic Disease
  • Disease Models, Animal
  • Hypothalamus / drug effects
  • Hypothalamus / physiopathology
  • Inflammatory Bowel Diseases / complications
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / physiopathology*
  • Male
  • Oxytocin / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Secretin / pharmacology*

Substances

  • Secretin
  • Oxytocin