Neuron-specific Sumo1-3 knockdown in mice impairs episodic and fear memories.
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 articleSubject
BrainNeurons
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
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https://hdl.handle.net/10161/23277Published Version (Please cite this version)
10.1503/jpn.130148Publication 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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Show full item recordScholars@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
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
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
Wei Yang
Associate Professor in Anesthesiology
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