Apolipoprotein E is upregulated in olfactory bulb glia following peripheral receptor lesion in mice

Apolipoprotein E (apoE), a lipid transporting protein, has been postulated to participate in nerve regeneration. To better clarify apoE function in th e olfactory system, we evaluated the amount and distribution of apoE in the olfactory bulb following olfactory nerve lesion in mice. Olfactory nerve w as lesioned in 2-to 4-month-old mice by intranasal irrigation with Triton X -100. Olfactory bulbs were collected at 0, 3, 7, 21, 42, and 56 days postle sion, and both apoE concentrations and apoE distribution were determined. A poE levels, as determined by immunoblot analysis, were twofold greater than normal during nerve degeneration at 3 days. ApoE levels remained elevated by approximately 1.5 times normal levels at 7 through 21 days after injury and returned to baseline by 56 days. Immunocytochemical studies supported t hese observations. ApoE immunoreactivity was prominent on the olfactory ner ve at 3 days after lesion and decreased to baseline levels at later time pe riods. Double-labeling immunocytochemical studies confirmed that both react ive astroglia and microglia produced detectable amounts of apoE following t he lesion. Return of apoE expression to baseline paralleled measures of olf actory nerve maturation as measured by olfactory marker protein. These data suggest that apoE increases concurrent with nerve degeneration. ApoE may f acilitate efficient regeneration perhaps by recycling lipids from degenerat ing fibers for use by growing axons. The association of apoE genotype with dementing illnesses may represent a diminished ability to support a lifetim e of nerve regeneration. (C) 2001 Academic Press.