The Liver X Receptor Agonist GW3965 Improves Recovery from Mild Repetitive Traumatic Brain Injury in Mice Partly through Apolipoprotein E

• DOI: 10.1371/journal.pone.0053529
• Publication Date: 2013-01-17T22:12:20Z
• Authors: Dhananjay R. Namj...; Georgina Martin; James Donkin; Anna Wilkinson; Sophie Stukas; Jianjia Fan; Michael Carr; Sepideh Tabarestani; Kelli Wuerth; Robert E. W. Hancock; Cheryl L. Wellington
• Keywords: Liver X receptor; Apolipoprotein E

Traumatic brain injury (TBI) increases Alzheimer's disease (AD) risk and leads to the deposition of neurofibrillary tangles amyloid deposits similar those found in AD. Agonists Liver X receptors (LXRs), which regulate expression many genes involved lipid homeostasis inflammation, improve cognition reduce neuropathology AD mice. One pathway by LXR agonists exert their beneficial effects is through ATP-binding cassette transporter A1 (ABCA1)-mediated transport onto apolipoprotein E (apoE). To test therapeutic utility this for TBI, we subjected male wild-type (WT) apoE−/− mice mild repetitive traumatic (mrTBI) followed treatment with vehicle or agonist GW3965 at 15 mg/kg/day. restored impaired novel object recognition memory WT but not did significantly enhance spontaneous recovery motor deficits observed all groups. Total soluble Aβ40 Aβ42 levels were elevated after injury, a response that was suppressed both genotypes. showed significant axonal damage 2 d post-mrTBI, GW3965. In contrast, severe from 14 mrTBI unresponsive Because our model does produce are unlikely be related reduced inflammation. Rather, results suggest apoE-dependent apoE-independent pathways contribute ability promote mrTBI.