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Neuron-specific Sumo1-3 knockdown in mice impairs episodic and fear memories.

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Date
2014-07
Authors
Wang, Liangli
Rodriguiz, Ramona M
Wetsel, William C
Sheng, Huaxin
Zhao, Shengli
Liu, Xiaozhi
Paschen, Wulf
Yang, Wei
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Abstract
BACKGROUND:Growing evidence suggests that small ubiquitin-like modifier (SUMO) conjugation plays a key role in brain plasticity by modulating activity-dependent synaptic transmission. However, these observations are based largely on cell culture experiments. We hypothesized that episodic and fear memories would be affected by silencing SUMO1-3 expression. METHODS:To investigate the role of SUMO conjugation in neuronal functioning in vivo, we generated a novel Sumo transgenic mouse model in which a Thy1 promoter drives expression of 3 distinct microRNAs to silence Sumo1-3 expression, specifically in neurons. Wild-type and Sumo1-3 knockdown mice were subjected to a battery of behavioural tests to elucidate whether Sumoylation is involved in episodic and emotional memory. RESULTS:Expression of Sumo1-3 microRNAs and the corresponding silencing of Sumo expression were particularly pronounced in hippocampal, amygdala and layer V cerebral cortex neurons. The Sumo knockdown mice displayed anxiety-like responses and were impaired in episodic memory processes, contextual and cued fear conditioning and fear-potentiated startle. LIMITATIONS:Since expression of Sumo1-3 was silenced in this mouse model, we need to verify in future studies which of the SUMO paralogues play the pivotal role in episodic and emotional memory. CONCLUSION:Our results indicate that a functional SUMO conjugation pathway is essential for emotionality and cognition. This novel Sumo knockdown mouse model and the technology used in generating this mutant may help to reveal novel mechanisms that underlie a variety of neuropsychiatric conditions associated with anxiety and impairment of episodic and emotional memory.
Type
Journal article
Subject
Brain
Neurons
Animals
Mice, Inbred C57BL
Mice, Transgenic
Mice
MicroRNAs
Fluorescent Antibody Technique
In Situ Hybridization
Emotions
Anxiety
Fear
Conditioning (Psychology)
Cues
Memory
Neuropsychological Tests
Gene Silencing
Male
Gene Knockdown Techniques
Reflex, Startle
Permalink
https://hdl.handle.net/10161/23277
Published Version (Please cite this version)
10.1503/jpn.130148
Publication Info
Wang, Liangli; Rodriguiz, Ramona M; Wetsel, William C; Sheng, Huaxin; Zhao, Shengli; Liu, Xiaozhi; ... Yang, Wei (2014). Neuron-specific Sumo1-3 knockdown in mice impairs episodic and fear memories. Journal of psychiatry & neuroscience : JPN, 39(4). pp. 259-266. 10.1503/jpn.130148. Retrieved from https://hdl.handle.net/10161/23277.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Wulf Paschen

Professor in Anesthesiology
My research interests are understanding the mechanisms underlying induction of cell death induced by a severe form of cellular stress. I am particularly interested in the role of the endoplasmic reticulum in the pathological process induced by transient cerebral ischemia and culminating in neuronal cell death. This pathological process is associated with an irreversible suppression of protein synthese that limits the ability of cells to withstand ischemia-induced impairment of endoplasmic r
Sheng

Huaxin Sheng

Associate Professor in Anesthesiology
We have successfully developed various rodent models of brain and spinal cord injuries in our lab, such as focal cerebral ischemia, global cerebral ischemia, head trauma, subarachnoid hemorrhage, intracerebral hemorrhage, spinal cord ischemia and compression injury. We also established cardiac arrest and hemorrhagic shock models for studying multiple organ dysfunction.  Our current studies focus on two projects. One is to examine the efficacy of catalytic antioxidant in treating cerebral is
Wetsel

William Christopher Wetsel

Associate Professor in Psychiatry and Behavioral Sciences
RESEARCH INTERESTS Last Updated: 27 October 2020 My laboratory uses genetically-modified mice to study the roles that certain genes and gene products play in the presentation of abnormal neuroendocrine, neurological, and psychiatric responses. Traditionally, the identification of neuroendocrine dysfunction has involved biochemical analyses of hormonal responses, those for neurological disorders have relied upon behavioral and postmortem analyses, and those for psychiatric condi
Yang

Wei Yang

Associate Professor in Anesthesiology
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