Reconstitution of the olfactory epithelium following injury in apoE-deficient mice.
ApoE, a protein component of lipoproteins, is extensively expressed in the primary olfactory pathway. Because apoE has been shown to play a vital role in nerve repair and remodeling, we hypothesized that apoE expression will increase in the injured olfactory epithelium (OE), and that apoE deficiency in apoE knockout (KO) mice will lead to delayed/incomplete reconstitution of the OE following injury. To directly test this hypothesis, we compared OE regeneration in wild-type (WT) and KO mice following injury induced by intranasal irrigation of Triton X-100. OE was collected at 0, 3, 7, 21, 42, and 56 days post lesion. The amount and distribution of apoE in the regenerating OE was measured by immunoblotting and immunohistochemistry. Rate of OE reconstitution in WT and KO mice was assessed by using three independent measures: (1) OE thickness was measured in cresyl-violet stained sections, (2) basal cell proliferation was determined by using bromodeoxyuridine (BrdU) staining, and (3) differentiation and maturation of olfactory sensory neurons were measured by immunoblotting and immunohistochemical analysis of growth associated protein (GAP) 43 and olfactory marker protein (OMP). The results revealed that apoE expression in the OE is highly regulated during the entire course of OE reconstitution post injury, and that apoE deficiency in apoE KO mice leads to delayed recovery of mature OMP(+) cells in the reconstituting OE. The data suggest that apoE production increases in the injured OE to facilitate maturation of olfactory sensory neurons.
Nathan
Britto P
BP
Department of Biological Sciences, Eastern Illinois University, 600 Lincoln Avenue, Charleston, IL 61920, USA. bpnathan@eiu.edu
Gairhe
Salina
S
Nwosu
Ikemefuna
I
Clark
Stephen
S
Struble
Robert G
RG
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D000963:Antimetabolites; D001057:Apolipoproteins E / Q000235:genetics* / Q000502:physiology*; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002452:Cell Count; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000502:physiology; D019922:GAP-43 Protein / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009830:Olfactory Bulb / Q000378:metabolism; D051842:Olfactory Marker Protein / Q000096:biosynthesis / Q000235:genetics; D009831:Olfactory Mucosa / Q000166:cytology / Q000293:injuries* / Q000502:physiology*; D020127:Recovery of Function / Q000235:genetics / Q000502:physiology
D000199:Actins; D000963:Antimetabolites; D001057:Apolipoproteins E; D019922:GAP-43 Protein; D051842:Olfactory Marker Protein; D001973:Bromodeoxyuridine