cetrorelix and Memory-Disorders

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.

Topics: Amyloid beta-Peptides; Animals; Gonadotropin-Releasing Hormone; Hippocampus; Hormone Antagonists; Infusions, Intraventricular; Kisspeptins; Male; Memory Disorders; Mice; Peptide Fragments; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Receptors, LHRH; Recognition, Psychology; Retention, Psychology; Spatial Memory

Phoenixin (PNX) is a recently discovered neuropeptide shown to be involved in regulating the reproductive system, anxiety-related behaviors and pain though its receptor is still unknown. PNX-14, one of the endogenous active isoforms, is reported to regulate gonadotropin releasing hormone (GnRH) receptor expression and GnRH secretion. Because GnRH system is thought to be involved in the regulation of learning and memory processes, we hypothesized that PNX-14 might be mediate learning and memory. Here, we investigated the effects of PNX-14 in memory processes, using novel object recognition (NOR) and object location recognition (OLR) tasks. Our results revealed that intracerebroventricular (i.c.v.) injection of PNX-14 (25nmol) immediately after training not only facilitated memory formation, but also prolonged memory retention in both tasks. The memory-enhancing effects of PNX-14 were also seen when it was infused into the hippocampus. Moreover, these memory-improving effects of PNX-14 could be blocked by a GnRH receptor antagonist (Cetrorelix). The memory-improving effects of PNX-14 were not related to any effects on locomotor activity. Additionally, the results suggested that i.c.v. injection of PNX-14 mitigate the memory impairment induced by the amyloid-β1-42 (Aβ1-42) peptide and scopolamine. The present results indicate that PNX-14 facilitates memory formation and prolongs memory retention through activation of the GnRH receptor, and mitigates the memory-impairing effects of Aβ1-42 and scopolamine, suggesting that PNX-14 may be effective as a drug for enhancing memory and treating Alzheimer׳s disease.

Topics: Amyloid beta-Peptides; Animals; Gonadotropin-Releasing Hormone; Injections, Intraventricular; Male; Maze Learning; Memory; Memory Disorders; Mice; Peptide Fragments; Peptides; Scopolamine