mRNA up-regulation of MHC II and pivotal pro-inflammatory genes in normal brain aging.
In normal brain aging, CNS resident macrophages exhibit increased expression of major histocompatibility complex (MHC) II expression. However, the transcriptional basis for this observation has not been clarified nor have age-related alterations in pivotal pro-inflammatory genes been characterized. Age-related mRNA alterations in MHC II, MHC II accessory molecules and several pro-inflammatory mediators were measured in older (24 months) and younger (3 months) male F344xBN F1 rats. Real time RT-PCR was utilized to measure steady state mRNA levels in hippocampus. Older as compared to younger animals exhibited increased mRNA levels of MHC II, CD86, CIITA and IFN-gamma. Furthermore, IL-10 and CD200 mRNA, molecules that down-regulate macrophage activation, was decreased in older animals. The present results indicate that normal brain aging is characterized by a shift towards a pro-inflammatory microenvironment in the CNS.
Frank
Matthew G
MG
Department of Psychology and Center for Neuroscience, University of Colorado at Boulder, Campus Box 345, Boulder, CO 80309-0345, USA. matt.frank@colorado.edu
Barrientos
Ruth M
RM
Biedenkapp
Joseph C
JC
Rudy
Jerry W
JW
Watkins
Linda R
LR
Maier
Steven F
SF
D000375:Aging / Q000235:genetics*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001921:Brain / Q000254:growth & development*; D017931:DNA Primers; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005802:Genes, MHC Class II / Q000235:genetics*; D007249:Inflammation / Q000235:genetics*; D008297:Male; D009474:Neurons / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification; D051381:Rats; D011916:Rats, Inbred F344; D011971:Receptors, Immunologic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000502:physiology
D015703:Antigens, CD; C495490:Cd200 protein, rat; D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C042739:antigens, CD200