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

Samuel W. Caito, Dejan Milatovic, Kristina E. Hill, Michael Aschner, Raymond F. Burk, William M. Valentine

Research output: Contribution to journalArticle

35 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalBrain Research
Volume1398
DOIs
StatePublished - Jun 29 2011
Externally publishedYes

Fingerprint

Selenoprotein P
Selenium
Brain
Weaning
Diet
Hippocampus
Somatosensory Cortex
Neurites
Silver
Medial Forebrain Bundle
Dendritic Spines
Neurologic Manifestations
Thalamus
Synaptic Transmission
Brain Stem
Homeostasis
Cell Death
Coloring Agents
Learning
Neurons

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 journalArticle

Caito, Samuel W. ; Milatovic, Dejan ; Hill, Kristina E. ; Aschner, Michael ; Burk, Raymond F. ; Valentine, William M. / Progression of neurodegeneration and morphologic changes in the brains of juvenile mice with selenoprotein P deleted. In: Brain Research. 2011 ; Vol. 1398. pp. 1-12.
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