Related Experiment Video
Updated: May 28, 2026
04:48
A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
NMDA receptor function, memory, and brain aging
J W Newcomer1, N B Farber, J W Olney
1Departement of Psychiatry, Washington University School of Medicine, St Louis, Mo, USA.
Dialogues in Clinical Neuroscience
|October 29, 2011
Summary
N-methyl-D-aspartate (NMDA) receptor hypofunction is linked to cognitive decline and brain injury, worsening with age and Alzheimer's disease. Interventions targeting NMDA receptor overstimulation may offer new Alzheimer's treatments.
Area of Science:
- Neuroscience
- Neurology
- Pathophysiology
Background:
- N-methyl-D-aspartate (NMDA) receptor hypofunction is implicated in cognitive impairments, psychosis, and excitotoxic brain injury.
- Age-related decline in NMDA receptor function contributes to reduced memory and learning.
- In Alzheimer's disease (AD) pathogenesis, amyloidopathy and oxidative stress exacerbate NMDA receptor hypofunction (NRHypo).
Purpose of the Study:
- To explore the role of increasing NMDA receptor hypofunction in cognitive decline and neurodegeneration.
- To investigate the interaction of aging and AD-specific pathologies in exacerbating NRHypo.
- To propose potential therapeutic strategies targeting NMDA receptor overstimulation for AD prevention and treatment.
Main Methods:
- Review and synthesis of existing research on NMDA receptor function in aging and Alzheimer's disease.
- Hypothesizing the progression from NRHypo to severe neurodegeneration in vulnerable individuals.
- Utilizing findings from an animal model of neuronal overstimulation.
Main Results:
- Progressive hypofunction of the NMDA receptor system occurs with brain aging, impacting cognitive performance.
- In individuals predisposed to AD, combined pathologies significantly increase the NRHypo burden.
- Severe and persistent NRHypo states can precipitate widespread neurodegeneration and cognitive deterioration.
Conclusions:
- NMDA receptor hypofunction is a critical factor in age-related cognitive decline and Alzheimer's disease progression.
- Understanding the mechanisms of NRHypo is crucial for developing effective AD treatments.
- Pharmacological interventions aimed at preventing corticolimbic pyramidal neuron overstimulation show promise for AD prevention and therapy.
Related Concept Videos
01:23Role of Neurotransmitters in Memory
Neurotransmitters are integral to the brain's communication system, enabling neurons to transmit signals across synapses. This chemical exchange underpins various cognitive functions, including memory processes. The role of neurotransmitters in memory is multifaceted, influencing the encoding, consolidation, and retrieval of memories through their action on different neural circuits.
Glutamate and Synaptic Plasticity
Glutamate, the brain's main excitatory neurotransmitter, is critical for...
Glutamate and Synaptic Plasticity
Glutamate, the brain's main excitatory neurotransmitter, is critical for...
01:30Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function. They...
01:05Long-term Depression
Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
01:03Long-term Depression
Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Calcium Ion Concentration Mechanism
If over time, all...
Calcium Ion Concentration Mechanism
If over time, all...
01:35Long-term Potentiation
Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre- and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
01:25Long-term Potentiation
Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
Hebbian LTP
LTP can occur when presynaptic neurons...
Hebbian LTP
LTP can occur when presynaptic neurons...