Differential Expression of Extracellular Matrix and Adhesion Molecule Genes in the Brain of Juvenile versus Adult Mice in Responses to Intracerebroventricular Administration of IL-1

Abstract

Objective: Intracerebroventricular (ICV) injection of interleukin-1 (IL-1) stimulates the recruitment of leukocytes into the central nervous system at different time points in juvenile versus adult mice. Our results showed that leukocytes entered brain parenchyma at 8 and 16 h after injection in juvenile and adult mice, respectively. This study compares the differential gene expression patterns of extracellular matrix and adhesion molecules in the brain of juvenile and adult mice. Methods: We analyzed these gene expressions in mice brains by microarray and real-time PCR at 2 and 8 h after ICV IL-1. Results: After ICV IL-1, the following genes were significantly upregulated in both juvenile and adult mice: LAMβ1-1, MMP17, TGFβ, THBS3 and VCAM1 were upregulated at 2 h after injection; LAMβ1-1 and TGFβ were upregulated at 8 h. Additional changes were found in adult mice only: CNTN1, ECM1, ICAM1 and LAMα4 were upregulated at 2 h after injection; COL4α1, MMP3 and VCAM1 were upregulated at 8 h; TIMP4 was downregulated. Comparing juvenile and adult mice, real-time PCR analysis showed that there was more induction of TGFβ at 8 h and a stronger downregulation of TIMP4 at 2 h after injection in juvenile mice. Higher expression of MMP17 was found in juvenile mice, compared to adult mice, at both 2 and 8 h after injection. Conclusions: These data show distinct expression patterns of molecules related to the extracellular matrix and adhesion molecules in juvenile versus adult mice, and suggest that increased expression of MMP17 and TGFβ and decreased expression of TIMP4 may contribute to the accelerated recruitment of leukocytes into the central nervous system in juvenile animals.