kiss1-protein--human and Memory-Disorders

Alzheimer's disease (AD) is a progressive neurological disease that slowly causing memory impairments with no effective treatment. We have recently reported that kisspeptin-13 (KP-13) ameliorates Aβ toxicity-induced memory deficit in rats. Here, the possible cellular impact of kisspeptin receptor activation in a rat model of the early stage AD was assessed using whole-cell patch-clamp recording from CA1 pyramidal neurons and molecular approaches. Compared to neurons from the control group, cells from the Aβ-treated group displayed spontaneous and evoked hyperexcitability with lower spike frequency adaptation. These cells had also a lower sag ratio in response to hyperpolarizing prepulse current delivered before a depolarizing current injection. Neurons from the Aβ-treated group exhibited short spike onset latency, lower rheobase and short utilization time compared with those in the control group. Furthermore, phase plot analysis of action potential showed that Aβ treatment affected the action potential features. These electrophysiological changes induced by Aβ were associated with increased expression of stromal interaction molecules (STIMs), particularly (STIM2) and decreased pCREB/CREB ratio. Treatment with KP-13 following Aβ injection into the entorhinal cortex, however, prevented the excitatory effect of Aβ on spontaneous and evoked neuronal activity, increased the latency of onset, enhanced the sag ratio, increased the rheobase and utilization time, and prevented the changes induced Aβ on spike parameters. In addition, the KP-13 application after Aβ treatment reduced the expression of STIMs and increased the pCREB/CREB ratio compared to those receiving Aβ treatment alone. In summary, these results provide evidence that activation of kisspeptin receptor may be effective against pathology of Aβ.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Hippocampus; Kisspeptins; Memory Disorders; Peptide Fragments; Pyramidal Cells; Rats; Rats, Wistar; Stromal Interaction Molecules

Topics: Animals; Avoidance Learning; Behavior, Animal; Brain; Conditioning, Classical; Fear; Gene Expression; Habenula; Kisspeptins; Male; Memory Disorders; Morphine; Odorants; Serotonin; Zebrafish; Zebrafish Proteins

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