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Chronic thrombin exposure results in an increase in apolipoprotein‐E levels
Author(s) -
Mhatre Molina,
Hensley Kenneth,
Nguyen Albert,
Grammas Paula
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20887
Subject(s) - apolipoprotein e , apolipoprotein b , thrombin , medicine , endocrinology , hippocampus , gene isoform , alzheimer's disease , chemistry , cholesterol , disease , biochemistry , platelet , gene
Studies have shown that individuals with both a history of traumatic brain injury and inheritance of apolipoprotein E‐4 (ApoE4) allele are associated with a poor neurologic outcome and an increased risk for Alzheimer's disease. We assessed the hypothesis that thrombin released during brain injury causes an increase in apolipoprotein‐E levels and such increase in the levels of apolipoprotein‐E4 isoform may have amyloidogenic effects. Rats received either thrombin (100 nm, 0.25 μl/hr, 28 days) or vehicle via intracerebroventricular (i.c.v.) infusion. Thrombin treatment increased apolipoprotein‐E levels in hippocampus as compared to vehicle treatment ( P < 0.001). Infusion of human apolipoprotein‐E4 (0.6 ng/hr, i.c.v., 56 days) into rats resulted in β‐amyloid deposition and increased the number of GFAP‐positive astrocytes. ApoE4 infusion also resulted in significant spatial memory deficits. These findings suggest that thrombin released during brain injury may contribute to an increase in apolipoprotein‐E levels. Such increase in Apolipoprotein‐E4 isoform facilitates β‐amyloid deposition and cognitive deficits. © 2006 Wiley‐Liss, Inc.