TY - JOUR
T1 - Enhancement of anxiety, facilitation of avoidance behavior, and occurrence of adult-onset obesity in mice lacking mitochondrial cyclophilin D
AU - Luvisetto, S.
AU - Basso, E.
AU - Petronilli, V.
AU - Bernardi, P.
AU - Forte, M.
PY - 2008/8/26
Y1 - 2008/8/26
N2 - In this report, we have assessed the behavioral responses of mice missing the Ppif gene (CyPD-KO), encoding mitochondrial cyclophilin D (CyPD). Mitochondrial CyPD is a key modulator of the mitochondrial permeability transition which is involved in the regulation of calcium- and oxidative damage-induced cell death. Behavioral screening of CyPD-KO mice (ranging between 4 and 15 months of age) was accomplished using a battery of behavioral paradigms which included testing of motor functions, exploratory activity, and anxiety/emotionality, as well as learning and memory skills. We found that, compared with wild-type mice, CyPD-KO mice were (i) more anxious and less explorative in open field and elevated plus maze and (ii) performed better in learning and memory of avoidance tasks, such as active and passive avoidance. However, the absence of CyPD did not alter the nociceptive threshold for thermal stimuli. Finally, deletion of CyPD caused also an abnormal accumulation of white adipose tissue resulting in adult-onset obesity, which was not dependent on increased food and/or water intake. Taken together, our results suggest a new fundamental role of mitochondrial CyPD in basal brain functions and body weight homeostasis.
AB - In this report, we have assessed the behavioral responses of mice missing the Ppif gene (CyPD-KO), encoding mitochondrial cyclophilin D (CyPD). Mitochondrial CyPD is a key modulator of the mitochondrial permeability transition which is involved in the regulation of calcium- and oxidative damage-induced cell death. Behavioral screening of CyPD-KO mice (ranging between 4 and 15 months of age) was accomplished using a battery of behavioral paradigms which included testing of motor functions, exploratory activity, and anxiety/emotionality, as well as learning and memory skills. We found that, compared with wild-type mice, CyPD-KO mice were (i) more anxious and less explorative in open field and elevated plus maze and (ii) performed better in learning and memory of avoidance tasks, such as active and passive avoidance. However, the absence of CyPD did not alter the nociceptive threshold for thermal stimuli. Finally, deletion of CyPD caused also an abnormal accumulation of white adipose tissue resulting in adult-onset obesity, which was not dependent on increased food and/or water intake. Taken together, our results suggest a new fundamental role of mitochondrial CyPD in basal brain functions and body weight homeostasis.
KW - conditioning avoidance
KW - food/water intake
KW - mitochondrial permeability transition
KW - open field
KW - plus maze
KW - rotarod
UR - http://www.scopus.com/inward/record.url?scp=49449113953&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=49449113953&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2008.06.030
DO - 10.1016/j.neuroscience.2008.06.030
M3 - Article
C2 - 18621101
AN - SCOPUS:49449113953
SN - 0306-4522
VL - 155
SP - 585
EP - 596
JO - Neuroscience
JF - Neuroscience
IS - 3
ER -