NMDA receptor function plays a major role in memory, cognition, mood, and more. This article starts off with straight research – warning – it’s not easy reading. However, later on, we break it down into something more palatable for the average reader.
Loss of NMDA receptor function in dopamine neurons leads to the development of effective disorder-like symptoms.
The role of changes in dopamine neuronal activity during the development of symptoms in affective disorders remains controversial.
Here, we show that the inactivation of NMDA receptors on dopaminergic neurons in adult mice led to the development of effective disorder-like symptoms. The loss of NMDA receptors altered activity and caused complete NMDA-insensitivity in dopamine-like neurons. Mutant mice exhibited increased immobility in the forced swim test and a decrease in social interactions.
The mutation also led to reduced saccharin intake, however, the preference for sweet taste was not significantly decreased. Additionally, we found that while mutant mice were slower to learn instrumental tasks, they were able to reach the same performance levels, had normal sensitivity to feedback, and showed similar motivation to exert effort as control animals. Taken together these results show that inducing the loss of NMDA receptor-dependent activity in dopamine neurons is associated with the development of effective disorder-like symptoms.
An increasing level of N-methyl-D-aspartate (NMDA) receptor hypofunction within the brain is associated with memory and learning impairments, psychosis, and ultimately with excitotoxic brain injury.
As the brain ages, the NMDA receptor system becomes progressively hypofunctional, contributing to decreases in memory and learning performance. In those individuals destined to develop Alzheimer’s disease, other abnormalities (eg, amyloidopathy and oxidative stress) interact to increase the NMDA receptor hypofunction (NRHypo) burden.
In these vulnerable individuals, the brain then enters into a severe and persistent NRHypo state, which can lead to widespread neurodegeneration with accompanying mental symptoms and further cognitive deterioration. If the hypotheses described herein prove correct, treatment implications may be considerable.
Pharmacological methods for preventing the overstimulation of vulnerable corticolimbic pyramidal neurons developed in an animal model may be applicable to the prevention and treatment of Alzheimer’s disease.
The N-methyl-D-aspartate (NMDA) receptor is a ligand of glutamate, the primary excitatory neurotransmitter in the human brain. It plays an integral role in synaptic plasticity, which is a neuronal mechanism believed to be the basis of memory formation.
NMDA receptors also appear to have involvement in a process called excitotoxicity. Excitotoxicity may play a role in the pathophysiology of a variety of diseases such as epilepsy or Alzheimer’s disease. It’s easy to see NMDA receptor function plays a huge role in cognition and neurological aging.
The SImple Version of NMDA receptor function
You may have heard of NMDA receptors while learning about a disease or medication, but do you understand what they are and why they are important? NMDA receptor function plays a huge role in cognition and neurological aging.
First, it helps to understand what we mean by the receptor. In your brain, you’ve got a bunch of cells called neurons. These are the cells that send and receive the electrical impulses that control your body.
Neurons are specialized—each one only deals with certain types of information. So, for example, one neuron may process the information on pain and temperature but have nothing to do with visual perception or learning new information.
The chemicals that send information from neuron to neuron are called neurotransmitters. Some of the better-known ones include serotonin and dopamine. Neurotransmitters specialize in certain types of information, as well. For instance, serotonin is involved in the sleep cycle, while dopamine deals with movement and addiction.
For a neurotransmitter to move signals through a neuron, it first has to “unlock” it. That’s where receptors come in. Think of receptors as boat slips or ports on your computer. Not every boat fits in every slip, and not every cable fits in every port. Neurotransmitters have keys that open the locks on a neuron’s receptors, and that allow information to flow through your neurons. NMDA receptor function plays a major role
NMDA Receptor Function and Neurotransmitters
NMDA receptors can be activated (unlocked) by binding with an assortment of neurotransmitters, including:
NMDA receptors work with these neurotransmitters to rev up activity in areas of your brain that help you learn new information and form memories. They stimulate and “excite” the neurons. That’s a good thing, but only up to a point.
If the neurons stay in an excited state for too long, they can become overstimulated and start to function poorly. Eventually, they become so overexcited that they die.
That kind of overstimulation is called “excitotoxicity.” Glutamate and aspartate, in excess, are both classified as excitotoxins. To keep excitotoxicity from killing our brain cells, we also have neurotransmitters that calm the neurons. They’re called inhibitors.
Glycine, another one of the brain chemicals that bind with NMDA receptors, is an inhibitor in the spinal cord but is believed to be excitatory in the brain.
When our brains are healthy and functioning properly, excitatory and inhibitory neurotransmitters are generally able to keep things in balance so our neurons aren’t in jeopardy of overstimulation. However, when things aren’t working properly—i.e., a receptor is malfunctioning or neurotransmitter levels are out of balance—then we may start losing neurons to excitotoxicity.
Our bodies can’t make new neurons, so when they die, we’ve lost irreplaceable parts of our brains. It’s no surprise, then, that NMDA receptor function problems are believed to be involved in a wide variety of central nervous system conditions, including many that are neurodegenerative.
Illnesses Linked to NMDA Receptor Malfunction
Neurodegenerative diseases believed to be linked to NMDA receptors malfunction include:
- Alzheimer’s disease
- Amyotrophic lateral sclerosis (ALS)
- Huntington’s disease
- Parkinson’s disease
- Epilepsy
Other central nervous system conditions with suspected NMDA receptor function involvement include:
- Fibromyalgia
- Chronic fatigue syndrome
- Migraine aura
- Some types of headache
- Anxiety
- Depression
- Schizophrenia
- Post-traumatic stress disorder
- Obsessive-compulsive disorder
Some conditions that don’t involve NMDA receptor dysfunction may benefit from drugs that target NMDARs, such as:
- Phobia
- Stroke
- Pain from damaged nerves (neuropathy)
In phobias, NMDA receptor stimulating drugs are believed to help the amygdala (a part of the brain that deals with fear) re-learn new associations that help counter the fear.
In strokes, research suggests that inhibiting glutamate via NMDA receptors may help decrease damage to brain cells caused by a lack of oxygen.
In neuropathic pain, these drugs may help boost the effect of painkillers due to their involvement with the opioid pathways.
Treatments Targeting NMDA Receptor Function
Brain chemistry is a tricky thing, and throwing it out of whack can be extremely dangerous. Even if it seems logical that something could help with your symptoms, it’s crucial that you talk to a healthcare provider before trying anything that alters NMDA receptor function (or other aspects of how your brain works).
Many drugs and supplements are believed to alter the function of NMDA receptors. They come in two opposite forms: antagonists and agonists.
Taken together, our results and those described in other reports agree that decreases in the activity of the DA neurons in the ventral midbrain lead to changes in behaviors that resemble the symptoms of affective disorders.
Moreover, the reverse may also be true, in that procedures that cause a depressive-like phenotype in rodents also cause a decrease in the activity of midbrain DA neurons.
Importantly, research data shows that at a molecular level, loss of NMDA receptor-dependent activity, and most probably its effect on burst activity, was responsible for specific changes in behavior, including despair-like behaviors, reduced social activity
NMDA Receptor Function Antagonists
You’re probably more familiar with the term “antagonist” when it refers to the villain of a story—the character who tries to slow down or block the hero from accomplishing his or her goals. In the medical sense, antagonists are drugs that slow or block things.
In the case of NMDA receptors, antagonists inhibit reception, meaning that they block neurotransmitters from unlocking these receptors. Many neurodegenerative diseases and other central nervous system disorders are sometimes treated with these types of medications.
DripDok NMDA Proprietary Blends
Supplements in this category include:
- Agmatine
- Arginine
- Huperzine A
- Zinc
We use a blend of both supplements and non-supplements depending on your medical history, goals, and needs.
Knowing about NMDA receptors may help you gain a better understanding of your illness and possible treatments for it. Keep in mind that these receptors are part of an incredibly complex system—the human brain is one of the most complex systems that exist. Only a healthcare provider can properly diagnose and treat conditions that involve things like receptors and neurotransmitters.
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