TY - JOUR
T1 - A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Aβ25-35
AU - Alkam, Tursun
AU - Nitta, Atsumi
AU - Mizoguchi, Hiroyuki
AU - Itoh, Akio
AU - Nabeshima, Toshitaka
N1 - Funding Information:
This work was supported, in part, by the Japan-China Sasakawa Medical fellowship (For Tursun Alkam); by Uehara Memorial Foundation fellowship for Foreign Researchers in Japan (For Tursun Alkam); by a Grant-in-Aid for the 21st Century Center of Excellence Program “Integrated Molecular Medicine for Neuronal and Neoplastic Disorders” from the Ministry of Education, Culture, Sports, Science and Technology of Japan; by a Grant-in-Aid for Health Science Research on Regulatory Science of Pharmaceuticals and Medical Devices, and Comprehensive Research on Aging and Health from the Ministry of Health, Labor and Welfare of Japan; by Japan Canada Joint Health Research Program (Joint Project from Japan Society for the Promotion of Science); by a grant from the Brain research Center from 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea; and by a Smoking Research Foundation Grant for Biomedical Research.
PY - 2007/6/18
Y1 - 2007/6/18
N2 - Peroxynitrite (ONOO-)-mediated damage is regarded to be responsible for the cognitive dysfunction induced by amyloid beta protein (Aβ) in Alzheimer's disease (AD). In the present study, we examined the protective effects of rosmarinic acid (RA), a natural scavenger of ONOO-, on the memory impairment in a mouse model induced by acute i.c.v. injection of Aβ25-35. Mice daily received i.p. several doses of RA after the injection of Aβ25-35. RA prevented the memory impairments induced by Aβ25-35 in the Y maze test and novel object recognition task. RA, at the effective lowest dose (0.25 mg/kg), prevented Aβ25-35-induced nitration of proteins, an indirect indicator of ONOO- damage, in the hippocampus. At this dose, RA also prevented nitration of proteins and impairment of recognition memory induced by ONOO--i.c.v.-injection. Co-injection of the non-memory-impairing dose of ONOO- with Aβ25-35 blocked the protective effects of RA (0.25 mg/kg). These results demonstrated that the memory protective effects of RA in the neurotoxicity of Aβ25-35 is due to its scavenging of ONOO-, and that daily consumption of RA may protect against memory impairments observed in AD.
AB - Peroxynitrite (ONOO-)-mediated damage is regarded to be responsible for the cognitive dysfunction induced by amyloid beta protein (Aβ) in Alzheimer's disease (AD). In the present study, we examined the protective effects of rosmarinic acid (RA), a natural scavenger of ONOO-, on the memory impairment in a mouse model induced by acute i.c.v. injection of Aβ25-35. Mice daily received i.p. several doses of RA after the injection of Aβ25-35. RA prevented the memory impairments induced by Aβ25-35 in the Y maze test and novel object recognition task. RA, at the effective lowest dose (0.25 mg/kg), prevented Aβ25-35-induced nitration of proteins, an indirect indicator of ONOO- damage, in the hippocampus. At this dose, RA also prevented nitration of proteins and impairment of recognition memory induced by ONOO--i.c.v.-injection. Co-injection of the non-memory-impairing dose of ONOO- with Aβ25-35 blocked the protective effects of RA (0.25 mg/kg). These results demonstrated that the memory protective effects of RA in the neurotoxicity of Aβ25-35 is due to its scavenging of ONOO-, and that daily consumption of RA may protect against memory impairments observed in AD.
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U2 - 10.1016/j.bbr.2007.03.001
DO - 10.1016/j.bbr.2007.03.001
M3 - Article
C2 - 17420060
AN - SCOPUS:34248210710
SN - 0166-4328
VL - 180
SP - 139
EP - 145
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 2
ER -