Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1-12 |
| Number of pages | 12 |
| Journal | Brain Research |
| Volume | 1398 |
| DOIs | |
| State | Published - Jun 29 2011 |
| Externally published | Yes |
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Keywords
- Amino cupric silver stain
- Axonopathy
- Hippocampus morphology
- Selenium deficiency
- Selenoprotein P
ASJC Scopus subject areas
- Neuroscience(all)
- Clinical Neurology
- Developmental Biology
- Molecular Biology
Cite this
Progression of neurodegeneration and morphologic changes in the brains of juvenile mice with selenoprotein P deleted. / Caito, Samuel W.; Milatovic, Dejan; Hill, Kristina E.; Aschner, Michael; Burk, Raymond F.; Valentine, William M.
In: Brain Research, Vol. 1398, 29.06.2011, p. 1-12.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Progression of neurodegeneration and morphologic changes in the brains of juvenile mice with selenoprotein P deleted
AU - Caito, Samuel W.
AU - Milatovic, Dejan
AU - Hill, Kristina E.
AU - Aschner, Michael
AU - Burk, Raymond F.
AU - Valentine, William M.
PY - 2011/6/29
Y1 - 2011/6/29
N2 - 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.
AB - 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.
KW - Amino cupric silver stain
KW - Axonopathy
KW - Hippocampus morphology
KW - Selenium deficiency
KW - Selenoprotein P
UR - http://www.scopus.com/inward/record.url?scp=79958779555&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79958779555&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2011.04.046
DO - 10.1016/j.brainres.2011.04.046
M3 - Article
C2 - 21636077
AN - SCOPUS:79958779555
VL - 1398
SP - 1
EP - 12
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -