Strain-dependent behavioral alterations induced by peripheral interleukin-1 challenge in neonatal mice

Behav Brain Res. 2006 Jan 6;166(1):19-31. doi: 10.1016/j.bbr.2005.07.007. Epub 2005 Aug 30.

Abstract

Interleukin-1 (IL-1) is implicated in the pathogenesis of various psychiatric diseases. Peripheral administration of IL-1alpha to neonatal rats induces cognitive and behavioral abnormalities and, therefore, the IL-1alpha-treated animals might serve as a schizophrenia model. The present study assessed genetic influences on IL-1alpha-triggered behavioral impairments, using four different strains of neonatal mice, C3H/He, DBA/2, C57BL/6, and ddY. Neonatal treatments with IL-1alpha differentially altered adult behavioral/cognitive traits in a strain-dependent manner. IL-1alpha treatment decreased prepulse inhibition in DBA/2 and C57BL/6 mice but not in C3H/He and ddY. The treatment increased locomotor activity and startle responses in DBA/2 mice and, conversely, decreased startle responses in C3H/He mice. Behavioral alterations were most remarkable in DBA/2 mice but undetectable in ddY mice. The magnitudes of IL-1alpha actions differed between the brain and periphery and were influenced by mouse genetic background. The IL-1-triggered acute signaling, Ikappa-B degradation, was significant in the frontal cortex of DBA/2 mice and in the hypothalamus of C3H/He mice. An increase in brain p38 MAP kinase phosphorylation was also most marked in the DBA/2 strain. In contrast, subchronic influences of IL-1alpha injections failed to illustrate the strain-dependent behavioral alterations. The peripheral effects of IL-1alpha did not match the strain-dependency of the behavioral alterations, either. Acceleration of tooth eruption and eyelid opening as well as attenuation of weight gain was most marked in C3H/He mice and the induction of serum amyloid protein was the largest in ddY mice. Thus, the peripheral effects of IL-1alpha in DBA/2 mice were relatively inferior to those in the other strains. The present animal study suggests that, in early postnatal development, circulating IL-1alpha trigger brain cytokine signaling and produce distinct influences on later neurobehavioral traits, both depending on genetic background.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Behavior, Animal / drug effects*
  • Behavior, Animal / physiology
  • Blotting, Western / methods
  • Body Weight / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Calcium-Binding Proteins / metabolism
  • Drug Administration Schedule
  • Gene Expression Regulation, Developmental / drug effects
  • I-kappa B Proteins / metabolism
  • Immunoenzyme Techniques / methods
  • Inhibition, Psychological
  • Interleukin-1 / administration & dosage*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred Strains
  • Microfilament Proteins
  • Motor Activity / drug effects
  • Phosphorylation / drug effects
  • Recombinant Proteins / administration & dosage
  • Reflex, Acoustic / drug effects
  • Species Specificity
  • Time Factors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Aif1 protein, mouse
  • Calcium-Binding Proteins
  • I-kappa B Proteins
  • Interleukin-1
  • Microfilament Proteins
  • Recombinant Proteins
  • p38 Mitogen-Activated Protein Kinases