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Distinct Roles of Selenoproteins in Facilitating Synaptic Plasticity for Learning and Memory.
|Title:||Distinct Roles of Selenoproteins in Facilitating Synaptic Plasticity for Learning and Memory.|
|Authors:||Nguyen-Wu, Elizabeth Quynh-Mai D.|
|Contributors:||Cell & Molecular Biology (department)|
|Date Issued:||Aug 2017|
|Publisher:||University of Hawaiʻi at Mānoa|
|Abstract:||Selenium (Se) is a micronutrient essential for life and important for proper|
neurological and immune function, reproductive viability, and cardiovascular health. In
the body, it acts through incorporation into selenoproteins, which can function as
antioxidants that protect cells from oxidative damage and maintain many other cellular
functions. This dissertation focused on the roles of Selenoprotein P and M (Sepp1 and
SelM) in learning and memory.
Sepp1 is primarily thought to transport Se to the tissues, including the brain, for
synthesis of other selenoproteins. Sepp1 has been shown to colocalize with amyloid
beta plaques in postmortem brains from patients diagnosed with Alzheimer’s disease
(AD) (1). Sepp1-/- mice on selenium deficient diets have severe neurological
impairments with major motor function deficits, and impaired hippocampal dependent
synaptic function and memory, similar to deficits seen in AD. We hypothesize that
Sepp1 has a localized function in the brain, independent of its function in transporting
selenium to the brain and other body tissues.
SelM has antioxidant properties and is highly expressed in the brain (2). The
hippocampus, one of the areas in which SelM is expressed, is involved in learning and
memory acquisition. A study using an AD mouse model having a mutant form of
presenilin-2 resulted in suppression of SelM expression (3). We report here that SelM-/-
male, but not female mice, lack hippocampal long-term potentiation (LTP), which is a
cellular model for learning and memory. These results suggest that SelM has an integral
sex-specific role in synaptic plasticity, learning and memory.
To determine the direct role for Sepp1 in the brain, we developed a novel mouse
model that has restored SEPP1 expression in forebrain neurons of Sepp1-/- mice. The
successful restoration of LTP in Sepp1-/- mice with locally restricted SEPP1 gene rescue
to forebrain neurons highlights the critical role Sepp1 plays in synaptic plasticity as well
as enabling synthesis of SelM and other selenoproteins that are required for learning
and memory. We elucidate the important neuroprotective properties of these
selenoproteins in memory and learning, serving as a foundation for further studies to
understand their roles in Alzheimer's disease and other neurodegenerative disorders.
|Description:||Ph.D. Thesis. University of Hawaiʻi at Mānoa 2017.|
|Rights:||All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.|
|Appears in Collections:||
Ph.D. - Cell and Molecular Biology|
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