Delayed olfactory nerve regeneration in ApoE-deficient mice

Nathan, Britto P.; Nisar, Rafia; Short, Jody; Randall, Shari; Grissom, Elin M.; Griffin, G. A. Elmer; Switzer, Paul; Struble, Robert G.

doi:10.1016/j.brainres.2005.02.011

Cited by 27 publications

(22 citation statements)

References 63 publications

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“…In contrast, Syn recovery in the KO mice did not reach comparability even by 56 days. This parallels our previous paper showing slower recovery in olfactory marker protein (OMP, mature ORN marker) and glomerular area in KO mice when compared to WT mice [14]. Hence, in the absence of apoE, synaptic recovery in whole bulb samples is substantially delayed compared to WT mice.…”

supporting

confidence: 90%

“…We found a significant interaction of day post lesion and glomerular area (F 7,32 =3.62; p<0.006). As shown previously, glomerular area was slower to recover in KO mice than WT mice and recovery in KO mice occurred between 42 and 56 days post lesion while the WT mice were essentially normal by 42 days [14]. We multiplied this glomerular area by Syn density, which is roughly analogous to measuring total number or size of glomerular synapses, and found a significant main effect of genotype (F 1,32 =25.27; p<0.001) and day (F 7,32 =21.10; p<0.001).…”

supporting

confidence: 77%

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Impact of apoE deficiency during synaptic remodeling in the mouse olfactory bulb

Nwosu

Gairhe

Struble

et al. 2008

Neuroscience Letters

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In this study we examined the role of apoE on the rate of synaptic recovery in the olfactory bulb (OB) following olfactory epithelium (OE) lesioning in mice. We used both immunoblotting and immunohistochemical techniques to compare the density of OB synaptophysin (Syn, a synaptic marker) in apoE-gene deficient/knockout (KO) mice and wild-type (WT) mice following OE lesion. We found that the whole bulb concentrations of Syn, measured by immunoblotting, declined sharply following injury in both WT and KO mice during the degenerative phase (3-7 days). After this initial decline, the Syn concentration gradually increased to normal levels by 56 days in WT mice. In contrast, Syn concentration in KO mice did not recover by day 56 when Syn density in WT was essentially normal. Glomerular Syn density, measured by immunohistochemistry, found a lower density in KO mice at all time points post lesion. This lower concentration of whole bulb Syn parallels the slower recovery of glomerular area in KO mice. The data indicate that apoE deficiency in KO mice is associated with a delayed recovery of the glomerular area and a slower recovery in Syn concentration in the OB. Keywords apoE; synaptophysin; olfactory bulb; glia; olfactory nerve; glial proteins; transgenic mice Apolipoprotein E (apoE), a lipid transporting protein, is widely expressed in the primary olfactory pathway [6,12,13,23,25]. Previous studies from our laboratories and others have shown apoE expression in the olfactory nerve and around the glomeruli in the OB of adult mice [12,23]. ApoE levels in the OB were two fold higher than normal immediately following OE lesion, and remained elevated over a 3-week period when axons from the newly differentiated olfactory receptor neurons (ORN) grew to reestablish the synaptic connections with cells in the glomeruli [13]. The precise function of apoE in the olfactory system during normal and injury-induced remodeling is unclear; however, studies suggest a role for apoE in the synaptogenesis of the CNS [2,8,20,27].

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supporting

confidence: 90%

supporting

confidence: 77%

Impact of apoE deficiency during synaptic remodeling in the mouse olfactory bulb

Nwosu

Gairhe

Struble

et al. 2008

Neuroscience Letters

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“…We reported a striking qualitative and quantitative increase of apoE in the olfactory nerve and bulb concurrent with olfactory nerve degeneration (Nathan et al, 2001). In addition, we found that olfactory nerve regeneration and recovery in the OB following OE lesion were significantly delayed in mice lacking apoE (Nathan et al, 2005). Reappearance of OMP in the OB following reversible lesion of OE in normal mice occurred between 7 and 21 days post lesion, reaching statistically normal levels by 42 days.…”

Section: Discussionmentioning

confidence: 78%

“…We have previously shown that apoE surrounds glomeruli of the olfactory bulb (OB) (Struble et al, 1999). Subsequent studies found that olfactory nerve regeneration and morphological recovery of the OB were significantly delayed in mice lacking apoE/knockout (KO) compared to wild-type (WT) mice following OE lesioning (Nathan et al, 2005). The olfactory nerve undergoes constant regeneration and axonal growth throughout the life of the organism (Graziadei and Graziadei, 1979;Graziadei and Monti Graziadei, 1985).…”

Section: Introductionmentioning

confidence: 99%

The distribution of apolipoprotein E in mouse olfactory epithelium

Nathan¹,

Nannapaneni²,

Gairhe³

et al. 2007

Brain Research

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Previous studies from our laboratory suggest that apolipoprotein (apoE), a lipid transporting protein, facilitates olfactory nerve regeneration. We have shown that apoE is enriched in the olfactory nerve and around the glomeruli of the olfactory bulb (OB). The studies reported herein were undertaken to identify possible sources of apoE in the olfactory epithelium (OE). Immunoblotting results revealed apoE expression in the OE of wild-type (WT) mice, but not in apoE deficient/knockout (KO) mice. Immunohistochemical studies revealed that the perikarya and processes of sustentacular (Sus) cells expressed apoE-like immunoreactivity. Minimal neuronal apoE immunostaining was seen, although apoE was observed in the interstial spaces between olfactory receptor neurons (ORN). Substantial apoE-like immunoreactivity was localized to the endfeet and terminal process of Sus cells surrounding the basal cells. Double labeling immunocytochemical studies confirmed that the cell bodies and endfeet of Sus cells expressed high levels of apoE. The endothelial cells of blood vessels were intensely stained for apoE in the lamina propria. Cells forming Bowman's gland also immunostained for apoE. The apoE staining in the nerve fascicles was less intense, but was uniformly distributed throughout the core of the nerve bundles. Heavily stained cells, probably ensheathing glia, surrounded the nerve fascicles. These results revealed that apoE is expressed in the adult OE and lamina propria at strategic locations where it could facilitate the differentiation, maturation and axonal growth of the ORN, perhaps by recycling lipids from degenerating ORN for use by growing axons.

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“…Interestingly, recent studies in APOE knockout mice have provided evidence for a role for APOE in the olfactory process,33 with APOE deficiency leading to substantial delay in olfactory nerve repair 34. APOE has been shown to be expressed at high levels in…”

mentioning

confidence: 99%