title: Kisspeptin-13 enhances memory and mitigates memory impairment induced by Aβ1-42 in mice novel object and object location recognition tasks.
abstract: Kisspeptin (KP), the endogenous ligand of GPR54, is a recently discovered neuropeptide shown to be involved in regulating reproductive system, anxiety-related behavior, locomotion, food intake, and suppression of metastasis across a range of cancers. KP is transcribed within the hippocampus, and GPR54 has been found in the amygdala and hippocampus, suggesting that KP might be involved in mediating learning and memory. However, the role of KP in cognition was largely unclear. Here, we investigated the role of KP-13, one of the endogenous active isoforms, in memory processes, and determined whether KP-13 could mitigate memory impairment induced by Aβ1-42 in mice, using novel object recognition (NOR) and object location recognition (OLR) tasks. Intracerebroventricular (i.c.v.) infusion of KP-13 (2μg) immediately after training not only facilitated memory formation, but also prolonged memory retention in both tasks. The memory-improving effects of KP-13 could be blocked by the GPR54 receptor antagonist, kisspeptin-234 (234), and GnRH receptors antagonist, Cetrorelix, suggesting pharmacological specificity. Then the memory-enhancing effects were also presented after infusion of KP-13 into the hippocampus. Moreover, we found that i.c.v. injection of KP-13 was able to reverse the memory impairment induced by Aβ1-42, which was inhibited by 234. To sum up, the results of our work indicate that KP-13 could facilitate memory formation and prolong memory retention through activation of the GPR54 and GnRH receptors, and suppress memory-impairing effect of Aβ1-42 through activation of the GPR54, suggesting that KP-13 may be a potential drug for enhancing memory and treating Alzheimer's disease.
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou 730000, China.
authors.forename: J H
authors.initials: JH
authors.lastname: Jiang
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou 730000, China.
authors.forename: Z
authors.initials: Z
authors.lastname: He
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou 730000, China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Peng
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou 730000, China.
authors.forename: W D
authors.initials: WD
authors.lastname: Jin
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou 730000, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang 330088, China.
authors.forename: R W
authors.initials: RW
authors.lastname: Han
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou 730000, China. Electronic address: changmin@lzu.edu.cn.
authors.forename: M
authors.initials: M
authors.lastname: Chang
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou 730000, China. Electronic address: wangrui@lzu.edu.cn.
authors.forename: R
authors.initials: R
authors.lastname: Wang
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D057967:Infusions, Intraventricular; D059648:Kisspeptins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000074502:Receptors, Kisspeptin-1; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects; D012153:Retention, Psychology / Q000187:drug effects; D065852:Spatial Memory / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D006727:Hormone Antagonists; C492248:Kiss1r protein, mouse; D059648:Kisspeptins; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D011966:Receptors, LHRH; C075222:amyloid beta-protein (1-42); C581520:kisspeptin-13, mouse; D007987:Gonadotropin-Releasing Hormone; C062876:cetrorelix
keywords: Aβ(1–42); GPR54; GnRH; Hippocampus; Kisspeptin-13; Recognition memory