We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Neuroprotective Effects of Ferrostatin and Necrostatin Against Entorhinal Amyloidopathy-Induced Electrophysiological Alterations Mediated by voltage-gated Ca<sup>2+</sup> Channels in the Dentate Gyrus Granular Cells.
- Authors
Naderi, Soudabeh; Motamedi, Fereshteh; Pourbadie, Hamid Gholami; Rafiei, Shahrbanoo; Khodagholi, Fariba; Naderi, Nima; Janahmadi, Mahyar
- Abstract
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 Aβ25−35 neurotoxicity, and their specific inhibitors had attenuating effects on cognitive impairment induced by Aβ25−35 neurotoxicity. Here, we aimed to examine the impact of ferroptosis and necroptosis inhibition following the Aβ25−35 neurotoxicity on the neuronal excitability of dentate gyrus (DG) and the possible involvement of voltage-gated Ca2+ channels in their effects. After inducing Aβ25−35 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. Aβ25−35 neurotoxicity induced a considerable reduction in input resistance (Rin), 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 Ca2+ 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 Ca2+ channel current and neuronal function, which might take place in neurons during the development of AD.
- Subjects
CALCIUM channels; ENTORHINAL cortex; DENTATE gyrus; GRANULE cells; ALZHEIMER'S disease; ELECTROPHYSIOLOGY; NEURON development
- Publication
Neurochemical Research, 2024, Vol 49, Issue 1, p99
- ISSN
0364-3190
- Publication type
Article
- DOI
10.1007/s11064-023-04006-7