Premium
Treatment with dexamethasone and vitamin D 3 attenuates neuroinflammatory age‐related changes in rat hippocampus
Author(s) -
Moore Michelle,
Piazza Alessia,
Nolan Yvonne,
Lynch Marina A.
Publication year - 2007
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20433
Subject(s) - dexamethasone , medicine , endocrinology , proinflammatory cytokine , microglia , hippocampal formation , vitamin , tumor necrosis factor alpha , hippocampus , neuroinflammation , calcitriol receptor , interleukin , chemistry , cytokine , vitamin d and neurology , inflammation
Among the changes which occur in the brain with age is an increase in hippocampal concentration of proinflammatory cytokines like interleukin‐1β (IL‐1β) and an increase in IL‐1β‐induced signaling. Here we demonstrate that the increase in IL‐1β concentration is accompanied by an increase in expression of IL‐1 type I receptor (IL‐1RI) and an age‐related increase in microglial activation, as shown by increased expression of the cell surface marker, major histocompatibility complex II (MHCII) and increased MHCII staining. The evidence indicates that these age‐related changes were abrogated in hippocampus of aged rats treated with dexamethasone and vitamin D 3 . Similarly, the age‐related increases in activation of the stress‐activated protein kinase, c‐Jun N‐terminal kinase (JNK), as well as caspase‐3 and PARP were all attenuated in hippocampal tissue prepared from rats that received dexamethasone and vitamin D 3 . The data indicate that dexamethasone and vitamin D 3 ameliorated the age‐related increase in IFNγ and suggest that IFNγ may be the trigger leading to microglial activation, since it increases MHCII mRNA and IL‐1β release from cultured glia. In parallel with its ability to decrease microglial activation in vivo, we report that treatment of cultured glia with dexamethasone and vitamin D 3 blocked the lipopolysaccharide increased MHCII mRNA and IL‐1β concentration, while the IL‐1β‐induced increases in activation of JNK and caspase 3 in cultured neurons were also reversed by treatment with dexamethasone and vitamin D 3 . The data suggest that the antiinflammatory effect of dexamethasone and vitamin D 3 derives from their ability to downreguate microglial activation. Synapse 61:851–861, 2007. © 2007 Wiley‐Liss, Inc.