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Short-Term Amyloid Beta Application Decreased Glutamate Release, but Increased Glutamate Spillover in Hippocampal Neurons

Year 2023, Volume: 5 Issue: Supplement (1) - Innovations in Medicine and Healthcare in the 100th Year of the Republic, 187 - 91, 19.10.2023
https://doi.org/10.37990/medr.1348054

Abstract

Aim: Synaptic dysfunction is a characteristic linked with the early stages of Alzheimer's disease (AD), but the pathological mechanisms remain elusive. It was aimed to investigate how amyloid beta 42 (Abeta42) peptide affects miniature events mediated by glutamate release in hippocampal neurons.
Material and Methods: We performed all experiments in the primary cultured hippocampal neurons in control and Abeta42-treated neurons (24 h). Pharmacologically isolated miniature excitatory postsynaptic currents (mEPSCs) were obtained in whole-cell voltage-clamp configuration at – 70 mV. AMPAergic channel conductance and basic synaptic parameters were evaluated by performing peak-scaled variance analysis and cumulative event analysis and glutamate spillover is determined by application of DNQX.
Results: The oligomeric Abeta42 for 24h decreased the mEPSCs frequency (***p<0.001), while it has no any measurable effect on the amplitude of mEPSCs as well as unitary current and number of receptors. In addition, the incubation of neurons with oligomeric Abeta42 for 24h increased the glutamate spillover measured as baseline shift (***p<0.001).
Conclusion: The oligomeric form of the Abeta42 peptide has a significant effect on the presynaptic site of excitatory synapses in primary cultured hippocampal neurons. It lowers the release probability during short-term incubation, while it increases glutamate spillover.

Supporting Institution

University of Turin

Project Number

HIDE_RILO_22_01

Thanks

I express my gratitude to Dr. Andrea Marcantoni and Claudio Franchino for supplying me with primary hippocampal neuron cultures and the essential tools required for performing the experiments.

References

  • 2020 Alzheimer's disease facts and figures. Alzheimers Dement. 2020 Mar 10. doi: 10.1002/alz.12068. [Epub ahead of print].
  • Yamamoto K, Yamamoto R, Kato N. Amyloid β and amyloid precursor protein synergistically suppress large-conductance calcium-activated potassium channel in cortical neurons. Front Aging Neurosci. 2021;13:660319.
  • Hidisoglu E, Kantar D, Ozdemir S, Yargicoglu P. Cognitive dysfunctions and spontaneous EEG alterations induced by hippocampal amyloid pathology in rats. Adv Med Sci. 2022;67:328-37.
  • Hidisoglu E, Chiantia G, Franchino C, et al. The ryanodine receptor-calstabin interaction stabilizer S107 protects hippocampal neurons from GABAergic synaptic alterations induced by Abeta42 oligomers. J Physiol. 2022;600:5295-309.
  • Rowe CC, Ng S, Ackermann U, et al. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007;68:1718-25.
  • Ting JT, Kelley BG, Lambert TJ, et al. Amyloid precursor protein overexpression depresses excitatory transmission through both presynaptic and postsynaptic mechanisms. Proc Natl Acad Sci U S A. 2007;104:353-8.
  • Hidisoglu E, Kantar-Gok D, Er H, et al. Alterations in spontaneous delta and gamma activity might provide clues to detect changes induced by amyloid-beta administration. Eur J Neurosci. 2018;47:1013-23.
  • Shankar GM, Li S, Mehta TH, et al. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med. 2008;14:837-42.
  • Gavello D, Rojo-Ruiz J, Marcantoni A, et al. Leptin counteracts the hypoxia-induced inhibition of spontaneously firing hippocampal neurons: a microelectrode array study. Plos One. 2012;7:e41530.
  • Gavello D, Calorio C, Franchino C, et al. Early alterations of hippocampal neuronal firing induced by Abeta42. Cereb Cortex. 2018;28:433-46.
  • Russo I, Gavello D, Menna E, et al. p140Cap regulates GABAergic synaptogenesis and development of hippocampal inhibitory circuits. Cereb Cortex. 2019;29:91-105.
  • He Y, Wei M, Wu Y, et al. Amyloid beta oligomers suppress excitatory transmitter release via presynaptic depletion of phosphatidylinositol-4,5-bisphosphate. Nat Commun. 2019;10:1193.
  • Parodi J, Sepulveda FJ, Roa J, et al. Beta-amyloid causes depletion of synaptic vesicles leading to neurotransmission failure. J Biol Chem. 2010;285:2506-14.
  • Busche MA, Eichhoff G, Adelsberger H, et al. Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease. Science. 2008;321:1686-9.
  • Ghatak S, Dolatabadi N, Trudler D, et al. Mechanisms of hyperexcitability in Alzheimer's disease hiPSC-derived neurons and cerebral organoids vs isogenic controls. Elife. 2019;8:e50333.
  • Lerdkrai C, Asavapanumas N, Brawek B, et al. Intracellular Ca(2+) stores control in vivo neuronal hyperactivity in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2018;115:E1279-88.
  • Marcantoni A, Cerullo MS, Buxeda P, et al. Amyloid Beta42 oligomers up-regulate the excitatory synapses by potentiating presynaptic release while impairing postsynaptic NMDA receptors. J Physiol-London. 2020;598:2183-97.
Year 2023, Volume: 5 Issue: Supplement (1) - Innovations in Medicine and Healthcare in the 100th Year of the Republic, 187 - 91, 19.10.2023
https://doi.org/10.37990/medr.1348054

Abstract

Project Number

HIDE_RILO_22_01

References

  • 2020 Alzheimer's disease facts and figures. Alzheimers Dement. 2020 Mar 10. doi: 10.1002/alz.12068. [Epub ahead of print].
  • Yamamoto K, Yamamoto R, Kato N. Amyloid β and amyloid precursor protein synergistically suppress large-conductance calcium-activated potassium channel in cortical neurons. Front Aging Neurosci. 2021;13:660319.
  • Hidisoglu E, Kantar D, Ozdemir S, Yargicoglu P. Cognitive dysfunctions and spontaneous EEG alterations induced by hippocampal amyloid pathology in rats. Adv Med Sci. 2022;67:328-37.
  • Hidisoglu E, Chiantia G, Franchino C, et al. The ryanodine receptor-calstabin interaction stabilizer S107 protects hippocampal neurons from GABAergic synaptic alterations induced by Abeta42 oligomers. J Physiol. 2022;600:5295-309.
  • Rowe CC, Ng S, Ackermann U, et al. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007;68:1718-25.
  • Ting JT, Kelley BG, Lambert TJ, et al. Amyloid precursor protein overexpression depresses excitatory transmission through both presynaptic and postsynaptic mechanisms. Proc Natl Acad Sci U S A. 2007;104:353-8.
  • Hidisoglu E, Kantar-Gok D, Er H, et al. Alterations in spontaneous delta and gamma activity might provide clues to detect changes induced by amyloid-beta administration. Eur J Neurosci. 2018;47:1013-23.
  • Shankar GM, Li S, Mehta TH, et al. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med. 2008;14:837-42.
  • Gavello D, Rojo-Ruiz J, Marcantoni A, et al. Leptin counteracts the hypoxia-induced inhibition of spontaneously firing hippocampal neurons: a microelectrode array study. Plos One. 2012;7:e41530.
  • Gavello D, Calorio C, Franchino C, et al. Early alterations of hippocampal neuronal firing induced by Abeta42. Cereb Cortex. 2018;28:433-46.
  • Russo I, Gavello D, Menna E, et al. p140Cap regulates GABAergic synaptogenesis and development of hippocampal inhibitory circuits. Cereb Cortex. 2019;29:91-105.
  • He Y, Wei M, Wu Y, et al. Amyloid beta oligomers suppress excitatory transmitter release via presynaptic depletion of phosphatidylinositol-4,5-bisphosphate. Nat Commun. 2019;10:1193.
  • Parodi J, Sepulveda FJ, Roa J, et al. Beta-amyloid causes depletion of synaptic vesicles leading to neurotransmission failure. J Biol Chem. 2010;285:2506-14.
  • Busche MA, Eichhoff G, Adelsberger H, et al. Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease. Science. 2008;321:1686-9.
  • Ghatak S, Dolatabadi N, Trudler D, et al. Mechanisms of hyperexcitability in Alzheimer's disease hiPSC-derived neurons and cerebral organoids vs isogenic controls. Elife. 2019;8:e50333.
  • Lerdkrai C, Asavapanumas N, Brawek B, et al. Intracellular Ca(2+) stores control in vivo neuronal hyperactivity in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2018;115:E1279-88.
  • Marcantoni A, Cerullo MS, Buxeda P, et al. Amyloid Beta42 oligomers up-regulate the excitatory synapses by potentiating presynaptic release while impairing postsynaptic NMDA receptors. J Physiol-London. 2020;598:2183-97.
There are 17 citations in total.

Details

Primary Language English
Subjects Cellular Nervous System
Journal Section Original Articles
Authors

Enis Hidisoglu 0000-0002-1729-1209

Project Number HIDE_RILO_22_01
Publication Date October 19, 2023
Acceptance Date October 3, 2023
Published in Issue Year 2023 Volume: 5 Issue: Supplement (1) - Innovations in Medicine and Healthcare in the 100th Year of the Republic

Cite

AMA Hidisoglu E. Short-Term Amyloid Beta Application Decreased Glutamate Release, but Increased Glutamate Spillover in Hippocampal Neurons. Med Records. October 2023;5(Supplement (1):187-91. doi:10.37990/medr.1348054

17741

Chief Editors

Assoc. Prof. Zülal Öner
Address: İzmir Bakırçay University, Department of Anatomy, İzmir, Türkiye

Assoc. Prof. Deniz Şenol
Address: Düzce University, Department of Anatomy, Düzce, Türkiye

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