Neuroprotective Effects of Ferrostatin and Necrostatin Against Entorhinal Amyloidopathy-Induced Electrophysiological Alterations Mediated by voltage-gated Ca 2+ Channels in the Dentate Gyrus Granular Cells.

Autor: Naderi S; School of Medicine, Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Motamedi F; Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Pourbadie HG; Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran., Rafiei S; Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Khodagholi F; Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Naderi N; Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Janahmadi M; Neuroscience Research Center, Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Janahmadi@sbmu.ac.ir.
Jazyk: angličtina
Zdroj: Neurochemical research [Neurochem Res] 2024 Jan; Vol. 49 (1), pp. 99-116. Date of Electronic Publication: 2023 Aug 24.
DOI: 10.1007/s11064-023-04006-7
Abstrakt: Alzheimer's disease (AD) is a progressive neurodegenerative disease that is the main form of dementia. Abnormal deposition of amyloid-beta (Aβ) peptides in neurons and synapses cause neuronal loss and cognitive deficits. We have previously reported that ferroptosis and necroptosis were implicated in Aβ 25-35 neurotoxicity, and their specific inhibitors had attenuating effects on cognitive impairment induced by Aβ 25-35 neurotoxicity. Here, we aimed to examine the impact of ferroptosis and necroptosis inhibition following the Aβ 25-35 neurotoxicity on the neuronal excitability of dentate gyrus (DG) and the possible involvement of voltage-gated Ca 2+ channels in their effects. After inducing Aβ 25-35 neurotoxicity, electrophysiological alterations in the intrinsic properties and excitability were recorded by the whole-cell patch-clamp under current-clamp condition. Voltage-clamp recordings were also performed to shed light on the involvement of calcium channel currents. Aβ 25-35 neurotoxicity induced a considerable reduction in input resistance (R in ), accompanied by a profoundly decreased excitability and a reduction in the amplitude of voltage-gated calcium channel currents in the DG granule cells. However, three days of administration of either ferrostatin-1 (Fer-1), a ferroptosis inhibitor, or Necrostatin-1 (Nec-1), a necroptosis inhibitor, in the entorhinal cortex could almost preserve the normal excitability and the Ca 2+ currents. In conclusion, these findings suggest that ferroptosis and necroptosis involvement in EC amyloidopathy could be a potential candidate to prevent the suppressive effect of Aβ on the Ca 2+ channel current and neuronal function, which might take place in neurons during the development of AD.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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