Brainstem Axonal Degeneration in Mice with Deletion of Selenoprotein P

Valentine, William M.; Hill, Kristina E.; Austin, Lori M.; Valentine, Holly L.; Goldowitz, Daniel; Burk, Raymond F.

doi:10.1080/01926230500243045

Cited by 48 publications

(36 citation statements)

References 16 publications

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“…Normal function can be rescued with a diet supplemented with high levels of Se [24]. Although Se supplemented mice survive and appear normal, they exhibit severe brain stem axonal degeneration [30]. Recent evidence suggests SelP is transported into brain by the apolipoprotein E (ApoE) receptor, ApoER2.…”

Section: Discussionmentioning

confidence: 99%

Association of Selenoprotein P with Alzheimer's Pathology in Human Cortex

Bellinger

et al. 2008

JAD

111

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Selenium is known for its antioxidant properties, making selenoproteins candidate molecules for mitigation of neurological disorders in which oxidative stress has been implicated. The selenium transport protein, selenoprotein P, is essential for neuronal survival and function. We sought to determine whether selenoprotein P expression is associated with Alzheimer’s disease pathology. We examined postmortem tissue from individuals with the hallmark lesions of Alzheimer’s disease and individuals without these lesions. Selenoprotein P immunoreactivity was co-localized with amyloid-β plaques and neurofibrillary tangles. Dense-core and other non-diffuse amyloid-β plaques were nearly always associated with selenoprotein P immunopositive cells. Analysis of spatial distribution showed a significant association between amyloid-β plaques and selenoprotein P. Numerous cells also exhibited immunoreactivity to selenoprotein P and intraneuronal neurofibrillary tangles. Confocal microscopy confirmed co-localization of amyloid-β protein and selenoprotein P. These findings suggest an association of selenoprotein P with Alzheimer’s pathology.

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Section: Discussionmentioning

confidence: 99%

Association of Selenoprotein P with Alzheimer's Pathology in Human Cortex

Bellinger

et al. 2008

JAD

111

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“…The latter are NADPH-dependent enzymes that convert oxidized thioredoxin back to the dithiol form. The plasma protein selenoprotein P is important in delivering selenium to the brain; mice lacking this protein die with severe degeneration of motor neurons unless their diet is enriched with selenium [34].…”

Section: Selenoprotein Pmentioning

confidence: 99%

Role of Selenium on Calcium Signaling and Oxidative Stress-induced Molecular Pathways in Epilepsy

2009

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Epilepsy is one of the oldest neurological conditions known to humankind. It is known that oxidative stress and generation of reactive oxygen species are a cause and consequence of epileptic seizures. Although recent years have seen tremendous progress in the molecular biology and metabolism of selenium, we still know little about the cell type-specific and temporal pattern of selenium and its derivatives in the brain of epileptic humans and experimental animals. It has been suggested that some antiepileptic drug therapies such as valproic acid, deplete the total body selenium level and selenium-dependent glutathione peroxidase (GSH-Px) activity although therapy with a new epileptic drug, topiramate, activated GSH-Px activity in epileptic animals and humans. An observation of lower blood or tissue selenium level and GSH-Px activity in epileptic patients and animals compared to controls in recent publications may support the proposed crucial role of selenium level and GSH-Px activity in the pathogenesis of epilepsy. Selenium is incorporated into an interesting class of molecules known as selenoproteins that contain the modified amino acid, selenocysteine. There are signs of selenium and selenoprotein deficiency in the pathogenesis of epilepsy. In conclusion, there is convincing evidence for the proposed crucial role of selenium and deficiency of GSH-Px enzyme activity in epilepsy pathogenesis. Blood GSH-Px activities could be a reliable indicator of selenium deficiency in patients with epilepsy.

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“…Sepp1 delivers selenium to brain and testes through interaction with the apolipoprotein E receptor 2 (apoER2), and once in the cells, selenium is then incorporated into selenoproteins during their synthesis (Burk et al 2005; Burk et al 2009). Deletion of Sepp1 in mice decreases brain selenium levels and feeding these mice a selenium-deficient diet results in severe neurological impairments and death (Hill et al 2004; Valentine et al 2005; Valentine et al 2008). In our previous studies, we identified extensive axonal degeneration in the brainstem and thalamus of Sepp1 −/− mice fed a selenium-deficient diet for 14 days (Valentine et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Progression of neurodegeneration and morphologic changes in the brains of juvenile mice with selenoprotein P deleted

et al. 2011

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Selenoprotein P (Sepp1) is an important protein involved in selenium (Se) transport and homeostasis. Severe neurologic dysfunction develops in Sepp1 null mice (Sepp1−/−) fed a selenium-deficient diet. Sepp1−/− mice fed a selenium-deficient diet have extensive degeneration of the brainstem and thalamus, and even when supplemented with selenium exhibit subtle learning deficits and altered basal synaptic transmission and short-term plasticity in the CA1 region of the hippocampus. The goal of this study was to delineate the regional progression of neurodegeneration in the brain, determine the extent of neuronal cell death, and evaluate neurite structural changes within the hippocampus of Sepp1−/− mice. Whole brain serial sections of wild-type and Sepp1−/− mice maintained on selenium-deficient or supplemented diets over the course of 12 days from weaning were evaluated with amino cupric silver neurodegeneration stain. The neurodegeneration was present in all regions upon weaning and progressed over 12 days in Sepp1−/− mice fed selenium-deficient diet, except in the medial forebrain bundle and somatosensory cortex where the neurodegeneration developed post-weaning. The neurodegeneration was predominantly axonal, however the somatosensory cortex and lateral striatum showed silver-stained neurons. Morphologic analysis of the hippocampus revealed decreased dendritic length and spine density, suggesting that loss of Sepp1 also causes subtle changes in the brain that can contribute to functional deficits. These data illustrate that deletion of Sepp1, and presumably selenium deficiency in the brain, produce both neuronal and axonal degeneration as well as more moderate and potentially reversible neurite changes in the developing brain.

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Brainstem Axonal Degeneration in Mice with Deletion of Selenoprotein P

Cited by 48 publications

References 16 publications

Association of Selenoprotein P with Alzheimer's Pathology in Human Cortex

Association of Selenoprotein P with Alzheimer's Pathology in Human Cortex

Role of Selenium on Calcium Signaling and Oxidative Stress-induced Molecular Pathways in Epilepsy

Progression of neurodegeneration and morphologic changes in the brains of juvenile mice with selenoprotein P deleted

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