TY - JOUR
T1 - TRPM2 confers susceptibility to social stress but is essential for behavioral flexibility
AU - Andoh, Chihiro
AU - Nishitani, Naoya
AU - Hashimoto, Emina
AU - Nagai, Yuma
AU - Takao, Keizo
AU - Miyakawa, Tsuyoshi
AU - Nakagawa, Takayuki
AU - Mori, Yasuo
AU - Nagayasu, Kazuki
AU - Shirakawa, Hisashi
AU - Kaneko, Shuji
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Transient receptor potential melastatin 2 (TRPM2) is a Ca2+-permeable, nonselective cation channel and a member of the TRP channel superfamily that acts as a sensor of intracellular redox states. TRPM2 is widely distributed in many tissues and highly expressed in the brain, but the physiological roles of TRPM2 in the central nervous system remain unclear. In this study, TRPM2-deficient mice were examined in a series of behavioral tests. TRPM2-deficient mice did not significantly differ from wild-type littermates in muscle strength, light/dark transition test, rotarod, elevated plus maze, social interaction, prepulse inhibition, Y-maze, forced swim test, cued and contextual fear conditioning, and tail suspension test. In the Barnes circular maze, TRPM2-deficient mice learned the fixed escape box position at similar extent to wild-type littermates, suggesting normal reference memory. However, performance of the first reversal trial and probe test were significantly impaired in TRPM2-deficient mice. In the T-maze delayed alternation task, TRPM2 deficiency significantly reduced choice accuracy. These results indicate that TRPM2-deficient mice shows behavioral inflexibility. Meanwhile, social avoidance induced by repeated social defeat stress was significantly attenuated in TRPM2-deficient mice, suggesting that TRPM2 deficiency confers stress resiliency. Our findings indicate that TRPM2 plays an essential role in maintaining behavioral flexibility but it increases susceptibility to stress.
AB - Transient receptor potential melastatin 2 (TRPM2) is a Ca2+-permeable, nonselective cation channel and a member of the TRP channel superfamily that acts as a sensor of intracellular redox states. TRPM2 is widely distributed in many tissues and highly expressed in the brain, but the physiological roles of TRPM2 in the central nervous system remain unclear. In this study, TRPM2-deficient mice were examined in a series of behavioral tests. TRPM2-deficient mice did not significantly differ from wild-type littermates in muscle strength, light/dark transition test, rotarod, elevated plus maze, social interaction, prepulse inhibition, Y-maze, forced swim test, cued and contextual fear conditioning, and tail suspension test. In the Barnes circular maze, TRPM2-deficient mice learned the fixed escape box position at similar extent to wild-type littermates, suggesting normal reference memory. However, performance of the first reversal trial and probe test were significantly impaired in TRPM2-deficient mice. In the T-maze delayed alternation task, TRPM2 deficiency significantly reduced choice accuracy. These results indicate that TRPM2-deficient mice shows behavioral inflexibility. Meanwhile, social avoidance induced by repeated social defeat stress was significantly attenuated in TRPM2-deficient mice, suggesting that TRPM2 deficiency confers stress resiliency. Our findings indicate that TRPM2 plays an essential role in maintaining behavioral flexibility but it increases susceptibility to stress.
KW - Behavioral inflexibility
KW - Stress resiliency
KW - TRPM2
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U2 - 10.1016/j.brainres.2018.09.031
DO - 10.1016/j.brainres.2018.09.031
M3 - Article
C2 - 30273551
AN - SCOPUS:85054304629
SN - 0006-8993
VL - 1704
SP - 68
EP - 77
JO - Brain Research
JF - Brain Research
ER -