Endomorphin-1 attenuates Aβ42 induced impairment of novel object and object location recognition tasks in mice.
A growing body of evidence suggests that the agglomeration of amyloid-β (Aβ) may be a trigger for Alzheimer׳s disease (AD). Central infusion of Aβ42 can lead to memory impairment in mice. Inhibiting the aggregation of Aβ has been considered a therapeutic strategy for AD. Endomorphin-1 (EM-1), an endogenous agonist of μ-opioid receptors, has been shown to inhibit the aggregation of Aβ in vitro. In the present study, we investigated whether EM-1 could alleviate the memory-impairing effects of Aβ42 in mice using novel object recognition (NOR) and object location recognition (OLR) tasks. We showed that co-administration of EM-1 was able to ameliorate Aβ42-induced amnesia in the lateral ventricle and the hippocampus, and these effects could not be inhibited by naloxone, an antagonist of μ-opioid receptors. Infusion of EM-1 or naloxone separately into the lateral ventricle had no influence on memory in the tasks. These results suggested that EM-1 might be effective as a drug for AD preventative treatment by inhibiting Aβ aggregation directly as a molecular modifier.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China.
Rui-san
RS
Zhang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China.
Hong-jiao
HJ
Xu
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China.
Jin-hong
JH
Jiang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China.
Ren-wen
RW
Han
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China.
Min
M
Chang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China.
Ya-li
YL
Peng
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China.
Yuan
Y
Wang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China. Electronic address: wangrui@lzu.edu.cn.
Rui
R
Wang
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D057967:Infusions, Intraventricular; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D051379:Mice; D009270:Naloxone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage; D009842:Oligopeptides / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D021641:Recognition, Psychology / Q000187:drug effects* / Q000502:physiology
D016229:Amyloid beta-Peptides; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009842:Oligopeptides; D010446:Peptide Fragments; D017450:Receptors, Opioid, mu; C075222:amyloid beta-protein (1-42); C105293:endomorphin 1; D009270:Naloxone
Alzheimer׳s disease; Amyloid-β; Endomorphin-1; Recognition memory