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J Clin Exp Tox 2017 | Volume 1 | Issue 2
Toxicology and Pharmacology
November 01-02, 2017 | Toronto, Canada
International Conference on
Tet1 overexpression leads to anxiety-like behavior and enhanced fear memories via the activation of
calcium-dependent cascade through Egr1 expression in mice
Wookbong Kwon
1
, Jin-Kyung Kim
2
, Eungyung Kim
1
and
Myoung Ok Kim
1
1
Kyungpook National University, Republic of Korea
2
Daegu Health College, Republic of Korea
T
en-eleven translocation methylcytosine dioxygenase
1 (Tet1) initiates DNA demethylation by converting
5-methylcytosine (5-mC) to 5-hydroxymethylcytosine
(5-hmC) at CpG-rich regions of genes, which plays a key
role in adult neurogenesis and memory. In addition, the
overexpression of Tet1 with 5-hmC alteration in patients
with psychosis has also been reported, for instance in
schizophrenia and bipolar disorders. The mechanism
underlying Tet1 overexpression in the brain, however, is still
elusive. In the present study, we found that Tet1-transgenic
(Tet1-TG) mice displayed abnormal behaviors involving
elevated anxiety and enhanced
fearmemories.Weconfirmed
that Tet1 overexpression affected adult neurogenesis with
oligodendrocyte differentiation in the hippocampal dentate
gyrus of Tet1-TG mice. In addition, Tet1 overexpression
induced the elevated expression of immediate early genes
(IEGs), such as Egr1, c-fos, Arc, and Bdnf followed by the
activation of intracellular calcium signals (i.e., CamKII, ERK,
and CREB) in prefrontal and hippocampal neurons. The
expression of gamma-aminobutyric acid (GABA) receptor
subunits (Gabra2 and Gabra4) fluctuated in the prefrontal
cortex (PFC) and hippocampus. We evaluated the effects
of Tet1 overexpression on intracellular calcium-dependent
cascades by activating the Egr1 promoter
in vitro
. Tet1
enhanced Egr1 expression, which may have led to alterations
in Gabra2 and Gabra4 expression in neurons. Taken together,
we suggest that the Tet1 overexpression in our Tet1-TG mice
can be applied as an effective model to study various stress-
related diseases that show hyperactivation of intracellular
calcium-dependent cascades in the brain.
Speaker Biography
Wookbong Kwon is currently studying for PhD at Kyungpook National University in
Korea. His current laboratory is focusing on elucidating gene function and their relation
to diseases using various transgenic mice models.
e:
6funny@naver.com