Research ReportPhoenixin-14 enhances memory and mitigates memory impairment induced by Aβ1-42 and scopolamine in mice

- Central PNX-14 enhanced memory and prolonged memory retention.
- The memory-enhancing effects of PNX-14 were blocked by Cetrorelix.
- PNX-14 infused into the bilateral hippocampus enhanced memory.
- PNX-14 mitigated the memory impairment induced by Aβ1-42 or scopolamine.
- PNX-14 failed to make a significant increase in locomotor activity.

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 (25 nmol) 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.