Deregulation of Melatonin Receptors and Differential Modulation of After-Hyperpolarization and Ih Currents Using Melatonin Treatment Due to Amyloid-β-Induced Neurotoxicity in the Hippocampus.

Autor: Eslamizade MJ; Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Saffarzadeh F; Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Khatami S; Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Davoudi S; Neurophysiology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Soleimani Z; Neuroscience Research Center and Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Anajafi S; Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Khoshnazar A; Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Mehdizadeh M; Reproductive Sciences and Technology Research Center, Department of Anatomy, Iran University of Medical Sciences, Tehran, Iran., Mohammadi-Yeganeh S; Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Janahmadi M; Neuroscience Research Center and Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Jazyk: angličtina
Zdroj: Cell biochemistry and function [Cell Biochem Funct] 2024 Sep; Vol. 42 (7), pp. e4129.
DOI: 10.1002/cbf.4129
Abstrakt: Treatment with melatonin is routinely prescribed for its potent antioxidant and cognitive-promoting effects, nevertheless, it has yet to find neuromodulatory effects in normal and disease conditions. Therefore, to investigate its neuromodulatory mechanisms, melatonin was systemically administered over 10 consecutive days to both intracortical normal saline- and amyloid-β 1-42 (Aβ) peptide-injected rats. At the behavioral level, treatment with melatonin was associated with reduced efficacy in restoring Aβ-induced deficit in passive-avoidance memory. Whole-cell patch-clamp recordings from CA1 pyramidal neurons revealed that melatonin treatment reduced spontaneous and evoked intrinsic excitability in control rats while exerting a reduction of spontaneous, but not evoked activity, in the Aβ-injected group. Interestingly, treatment with melatonin enhances after-hyperpolarization in control, but not Aβ-injected rats. In contrast, our voltage-clamp study showed that Ih current is significantly enhanced by Aβ injection, and this effect is further strengthened by treatment with melatonin in Aβ-injected rats. Finally, we discovered that the transcription of melatonin receptors 1 (MT1) and 2 (MT2) is significantly upregulated in the hippocampi of Aβ-injected rats. Collectively, our study demonstrates that systemic treatment with melatonin has differential neuromodulation on CA1 neuronal excitability, at least in part, via differential effects on after-hyperpolarization and Ih currents due to Aβ-induced neurotoxicity.
(© 2024 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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