Kisspeptin-13 prevented the electrophysiological alterations induced by amyloid-beta pathology in rat: Possible involvement of stromal interaction molecules and pCREB.

Autor: Khonacha SE; Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Mirbehbahani SH; Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Rahdar M; Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Davoudi S; Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Borjkhani M; Department of Electrical Engineering, Urmia University of Technology, Urmia, Iran and International Center for Translational Eye Research (ICTER), Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland., Khodagholi F; Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Motamedi F; Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Janahmadi M; Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Janahmadi@sbmu.ac.ir.
Jazyk: angličtina
Zdroj: Brain research bulletin [Brain Res Bull] 2022 Jun 15; Vol. 184, pp. 13-23. Date of Electronic Publication: 2022 Mar 07.
DOI: 10.1016/j.brainresbull.2022.03.003
Abstrakt: 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.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: