Biomedical subjects

Robert G Struble

Publications and source records attributed to Robert G Struble.

5 recordsLinked to original sources

PubMed2005

Delayed olfactory nerve regeneration in ApoE-deficient mice.

Apolipoprotein E (apoE), a lipid transporting protein, is extensively expressed in the primary olfactory pathway, but its function is unknown. We previously reported increased apoE levels in the olfactory bulb (OB) following olfactory epithelium (OE) lesion in mice, and hypothesized that apoE may play a vital role in olfactory nerve (ON) regeneration. To directly test this hypothesis, we examined the rate of ON regeneration following OE lesion in apoE deficient/knockout (KO) and wild-type (WT) mice. OE was lesioned in 2- to 3-month-old mice by intranasal irrigation with Triton X-100 (TX). OB were collected at 0, 3, 7, 21, 42, and 56 days post-lesion. OB recovery was measured by both immunoblotting and immunohistochemical analysis of growth cone associated protein (GAP) 43 and olfactory marker protein (OMP). The results revealed that (1) OMP recovery in the OB was significantly slower in apoE KO compared to WT mice; (2) recovery of glomerular area was similarly slower; and (3) GAP43 increases and return to prelesion levels in the OB were slower in KO mice. Together, these results show that olfactory nerve regeneration is significantly slower in KO mice as compared to WT mice, suggesting apoE facilitates olfactory nerve regeneration.

Animals↗

PubMed2004

Olfactory function in apoE knockout mice.

Apolipoprotein E (apoE), a lipid transporting protein, has been shown to play a vital role in nerve repair and remodeling. Since the olfactory system is in a continuous state of remodeling, the present study tested the hypothesis that apoE is required for normal functioning of the olfactory system. Olfactory behavior of wild-type (WT) and apoE-deficient (apoE KO) mice was assessed by using three standard olfactory tests: (1) the buried food pellet (BFP) test; (2) the odor choice (OC) test; and (3) the odor cued taste avoidance (OCTA) test. ApoE KO mice performed poorly in all the three tests as compared to WT mice, although they learned the tasks at a rate comparable to WT mice. ApoE KO mice had a significantly longer latency to find the buried pellet than WT mice. In the OC experiment, apoE KO mice did not differentiate water from an odorant solution. Furthermore, in the OCTA test the apoE KO mice were significantly less successful than WT mice at avoiding water containing an odorant and a bad tastant. These data demonstrate that apoE deficiency in apoE KO mice leads to a deficit in olfactory function, suggesting an important role for apoE in the olfactory system.

Animals↗

PubMed2004

Estrogen facilitates neurite extension via apolipoprotein E in cultured adult mouse cortical neurons.

Literature review suggests a close relationship between estrogen and apolipoprotein E (ApoE) in the central nervous system. Epidemiology studies show that estrogen replacement therapy (ERT) decreases the morbidity from several chronic neurological diseases. Alleles of ApoE modify the risk for and progression of the same diseases. ApoE levels in the rodent brain vary during the estrous cycle and increase after 17beta-estradiol administration. Both estradiol and ApoE3, the most common isoform of human ApoE, increase the extent of neurite outgrowth in culture. Combined, these observations suggest a common mechanism whereby estrogen may increase ApoE levels to facilitate neurite growth. We tested this hypothesis by characterizing the effects of estradiol and ApoE isoforms on neurite outgrowth in cultured adult mouse cortical neurons. Estradiol increased ApoE levels and neurite outgrowth. ApoE2 increased neurite length more so than ApoE3 in the presence of estradiol. Estradiol had no effect on neurite outgrowth from mice lacking the ApoE gene or when only ApoE4, the isoform of ApoE that is associated with increased risk of neurological disease, was exogenously supplied. Cultures from mice transgenic for human ApoE3 or ApoE4 showed the same isoform-specific effect. Neuronal internalization of recombinant human ApoE3 was greater than ApoE4, and ApoE3 was more effective than ApoE4 in facilitating neuronal uptake of a fatty acid. We conclude that estradiol facilitates neurite growth through an ApoE-dependent mechanism. The effects of ERT on chronic neurological diseases may vary with ApoE genotype. The clinical use of ERT may require ApoE genotyping for optimal efficacy.

Age Factors↗

PubMed2003

Effect of Neuregen nutrient medium on survival of cortical neurons after aspiration lesion in rats.

OBJECT: During brain surgery, it would be beneficial to irrigate the surgical cavity with a solution that promotes neuronal growth and survival. The authors find that incubation of cultured neurons with normal saline, also known as buffered salts, which are often used in brain surgery in humans, does not support neuron survival. Neuregen is an optimized serum-free culture medium that promotes regeneration of adult rat and human central nervous system neurons in vitro. It includes balanced salts, glucose, amino acids, vitamins, essential fatty acids, hormones, antioxidants, and other ingredients. The authors hypothesize that brain lesions irrigated and soaked in Neuregen nutrients will have better neuron survival rates in deafferented regions than lesions irrigated with saline. METHODS: Lesioning of the rat fimbria-fornix area was achieved by aspiration through the cortex; animals were killed 4 weeks later. Brain sections were stained with cresyl violet for neuron counts in the medial septum and cortex. Treatment of the lesion cavity with Neuregen resulted in a 55% increase in neuron density in the septum compared with saline treatment (p = 0.02). Cortical lesions treated with Neuregen showed a 27% increase in neuron density compared with saline-treated lesions (p = 0.015); the neuron density in Neuregen-treated rat brains was equivalent to that seen with sham treatment. Efficacy of Neuregen with basic fibroblast growth factor (bFGF) was significantly better than with Dulbecco modified Eagle medium bFGF, but not better than Neuregen alone. Neuregen produced a coincidental fourfold reduction in glial fibrillary acidic protein immunoreactivity at 4 weeks compared with saline (p = 0.002), to levels equivalent to those found in sham lesions. CONCLUSIONS: These results indicate that a highly optimized nutrient medium promotes neuron survival after brain surgery.

Animals↗

PubMed2002

Apolipoprotein E4 inhibits, and apolipoprotein E3 promotes neurite outgrowth in cultured adult mouse cortical neurons through the low-density lipoprotein receptor-related protein.

The apolipoprotein E4 (apoE4) genotype is a major risk factor for Alzheimer's disease (AD); however, the mechanism is unknown. We previously demonstrated that apoE isoforms differentially modulated neurite outgrowth in embryonic neurons and in neuronal cell lines. ApoE3 increased neurite outgrowth whereas apoE4 decreased outgrowth, suggesting that apoE4 may directly affect neurons in the brain. In the present study we examined the effects of apoE on neurite outgrowth from cultured adult mouse cortical neurons to examine if adult neurons respond the same way that embryonic cells do. The results from this study demonstrated that (1) cortical neurons derived from adult apoE-gene knockout (apoE KO) mice have significantly shorter neurites than neurons from adult wild-type (WT) mice; (2) incubation of cortical neurons from adult apoE KO mice with human apoE3 increased neurite outgrowth, whereas human apoE4 decreased outgrowth in a dose-dependent fashion; (3) the isoform specific effects were abolished by incubation of the neurons with either receptor associated protein (RAP) or lactoferrin, both of which block the interaction of apoE-containing lipoproteins with the low-density lipoprotein receptor-related protein (LRP). These data suggest a potential mechanism whereby apoE4 may play a role in regenerative failure and accelerate the development of AD.

Alzheimer Disease↗