TY - JOUR
T1 - Nobiletin, a citrus flavonoid, improves cognitive impairment and reduces soluble Aβ levels in a triple transgenic mouse model of Alzheimer's disease (3XTg-AD)
AU - Nakajima, Akira
AU - Aoyama, Yuki
AU - Shin, Eun Joo
AU - Nam, Yunsung
AU - Kim, Hyoung Chun
AU - Nagai, Taku
AU - Yokosuka, Akihito
AU - Mimaki, Yoshihiro
AU - Yokoi, Tsuyoshi
AU - Ohizumi, Yasushi
AU - Yamada, Kiyofumi
N1 - Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Alzheimer's disease (AD), the most common form of dementia among the elderly, is characterized by the progressive decline of cognitive function. Increasing evidence indicates that the production and accumulation of amyloid β (Aβ), particularly soluble Aβ oligomers, is central to the pathogenesis of AD. Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from citrus peels, ameliorates learning and memory impairment in olfactory-bulbectomized mice, amyloid precursor protein transgenic mice, NMDA receptor antagonist-treated mice, and senescence-accelerated mouse prone 8. Here, we present evidence that this natural compound improves cognitive impairment and reduces soluble Aβ levels in a triple transgenic mouse model of AD (3XTg-AD) that progressively develops amyloid plaques, neurofibrillary tangles, and cognitive impairments. Treatment with nobiletin (30mg/kg) for 3 months reversed the impairment of short-term memory and recognition memory in 3XTg-AD mice. Our ELISA analysis also showed that nobiletin reduced the levels of soluble Aβ1-40 in the brain of 3XTg-AD mice. Furthermore, nobiletin reduced ROS levels in the hippocampus of 3XTg-AD as well as wild-type mice. These results suggest that this natural compound has potential to become a novel drug for the treatment and prevention of AD.
AB - Alzheimer's disease (AD), the most common form of dementia among the elderly, is characterized by the progressive decline of cognitive function. Increasing evidence indicates that the production and accumulation of amyloid β (Aβ), particularly soluble Aβ oligomers, is central to the pathogenesis of AD. Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from citrus peels, ameliorates learning and memory impairment in olfactory-bulbectomized mice, amyloid precursor protein transgenic mice, NMDA receptor antagonist-treated mice, and senescence-accelerated mouse prone 8. Here, we present evidence that this natural compound improves cognitive impairment and reduces soluble Aβ levels in a triple transgenic mouse model of AD (3XTg-AD) that progressively develops amyloid plaques, neurofibrillary tangles, and cognitive impairments. Treatment with nobiletin (30mg/kg) for 3 months reversed the impairment of short-term memory and recognition memory in 3XTg-AD mice. Our ELISA analysis also showed that nobiletin reduced the levels of soluble Aβ1-40 in the brain of 3XTg-AD mice. Furthermore, nobiletin reduced ROS levels in the hippocampus of 3XTg-AD as well as wild-type mice. These results suggest that this natural compound has potential to become a novel drug for the treatment and prevention of AD.
KW - 3XTg-AD
KW - Alzheimer's disease
KW - Memory
KW - Nobiletin
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=84928746754&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928746754&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2015.04.028
DO - 10.1016/j.bbr.2015.04.028
M3 - Article
C2 - 25913833
AN - SCOPUS:84928746754
SN - 0166-4328
VL - 289
SP - 69
EP - 77
JO - Behavioural Brain Research
JF - Behavioural Brain Research
ER -