Apolipoprotein E modifies the CNS response to injury via a histamine-mediated pathway. Neurol Res 2007 Apr;29(3):243-50
Date
05/19/2007Pubmed ID
17509222DOI
10.1179/016164107X158974Scopus ID
2-s2.0-34249058360 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
Recent evidence demonstrates that apolipoprotein E (apoE) influences the central nervous system (CNS) response to both acute and chronic injury. To address the mechanisms by which apoE influences neurological disease, we examined differential gene expression in the brains of apoE transgenic mice after closed head injury. Apart from confirming the knockout of apoE, the largest differential gene expression occurred for the interleukin-9 receptor (IL-9R), which was > 100-fold up-regulated in apoE-deficient versus wild-type mice. We observed a similar pattern of posttraumatic IL-9R up-regulation in APOE4 targeted replacement mice as compared with their APOE3 counterparts. This difference in gene expression was associated with increased neuronal protein expression of IL-9R in E4 animals compared with E3 as demonstrated by immunohistochemistry. The consequence of IL-9R binding in mast cells is the induction of proliferation and differentiation. This indirectly favors degranulation and release of histamine and inflammatory mediators, which have previously been demonstrated to exacerbate secondary neuronal injury. We found that apoE-deficient animals had increased levels of systemic histamine after injury and that pre-treatment with antihistamines improved functional outcomes in apoE-deficient but not wild-type animals after head injury. These results suggest that apoE modifies secondary neuronal injury caused by histamine release and are consistent with previous observations that apoE affects the CNS inflammatory response in an isoform-specific manner.
Author List
Mace BE, Wang H, Lynch JR, Moss J, Sullivan P, Colton H, Morgan K, Renauld JC, Laskowitz DTMESH terms used to index this publication - Major topics in bold
Analysis of VarianceAnimals
Apolipoproteins E
Central Nervous System
Craniocerebral Trauma
Enzyme-Linked Immunosorbent Assay
Gene Expression Profiling
Histamine
Interleukin-9
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Motor Activity
Oligonucleotide Array Sequence Analysis
Reaction Time
Receptors, Interleukin-9
Signal Transduction
Time Factors
Up-Regulation
