Strain-dependent behavioral alterations induced by peripheral interleukin-1 challenge in neonatal mice.
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.
Tsuda
Noriko
N
Division of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
Tohmi
Manavu
M
Mizuno
Makoto
M
Nawa
Hiroyuki
H
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004334:Drug Administration Schedule; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D007124:Immunoenzyme Techniques / Q000379:methods; D007266:Inhibition, Psychological; D007375:Interleukin-1 / Q000008:administration & dosage*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008840:Microfilament Proteins; D009043:Motor Activity / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D012022:Reflex, Acoustic / Q000187:drug effects; D013045:Species Specificity; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D020672:I-kappa B Proteins; D007375:Interleukin-1; D008840:Microfilament Proteins; D011994:Recombinant Proteins; D048051:p38 Mitogen-Activated Protein Kinases