Memantine protects the cultured rat hippocampal neurons treated by NMDA and amyloid β1-42
Nataliia M Rozumna1, Vita V Hanzha1, Elena A Lukyanetz1
1Department of Biophysics of Ion Channels, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine.
Abstract:
Alzheimer's disease (AD) is a devastating neurodegenerative condition with no effective treatments. Recent research highlights the role of NMDA receptors in AD development, as excessive activation of these receptors triggers excitotoxicity. Memantine, an NMDA receptor antagonist, shows promise in curbing excitotoxicity. What sets our study apart is our novel exploration of memantine's potential to protect hippocampal neurons from neurotoxicity induced by NMDA and amyloid β1-42, a hallmark of AD. To achieve this, we conducted a series of experiments using rat hippocampal cell cultures. We employed Hoechst and propidium iodide double staining to assess neuronal viability. Analyzing the viability of neurons in normal conditions compared to their status after 24 h of exposure to the respective agents revealed compelling results. The incubation of hippocampal neurons with NMDA or amyloid β1-42 led to a more than twofold increase in the number of apoptotic and necrotic neurons. However, when memantine was co-administered with NMDA or amyloid β1-42, we witnessed a notable augmentation in the number of viable cells. This unique approach not only suggests that memantine may act as a neuroprotective agent but also emphasizes the relevance of hippocampal neuron cultures as valuable models for investigating excitotoxicity and potential AD treatments.
Insights
Memantine protects hippocampal neurons from excitotoxicity caused by NMDA and amyloid-beta in Alzheimer's disease models. This study highlights memantine's neuroprotective potential for Alzheimer's disease treatments.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Alzheimer's disease (AD) is a neurodegenerative disorder with no effective treatments.
- NMDA receptor overactivation causes excitotoxicity, contributing to AD.
- Amyloid-beta (Aβ1-42) is a key hallmark of AD pathology.
Purpose of the Study:
- To investigate the neuroprotective effects of memantine against NMDA- and Aβ1-42-induced neurotoxicity.
- To evaluate memantine's efficacy in protecting hippocampal neurons.
Main Methods:
- Utilized rat hippocampal cell cultures.
- Assessed neuronal viability using Hoechst and propidium iodide double staining.
- Exposed neurons to NMDA, Aβ1-42, and memantine (alone and in combination).
Main Results:
- NMDA or Aβ1-42 exposure significantly increased neuronal apoptosis and necrosis (more than twofold).
- Co-administration of memantine with NMDA or Aβ1-42 notably increased the number of viable cells.
- Memantine demonstrated a protective effect against neurotoxicity.
Conclusions:
- Memantine exhibits neuroprotective properties against NMDA- and Aβ1-42-induced neurotoxicity.
- Hippocampal neuron cultures serve as a valuable model for studying excitotoxicity and potential AD therapies.
- Findings suggest memantine's potential as a therapeutic agent for Alzheimer's disease.
More Related Videos
08:27Establishment of a Valuable Mimic of Alzheimer's Disease in Rat Animal Model by Intracerebroventricular Injection of Composited Amyloid Beta Protein
Published on: July 29, 2018
06:23Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons
Published on: October 30, 2018
Related Concept Videos
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
Alzheimer's Disease: Treatment
