Skip to main content

D-Serine as the gatekeeper of NMDA receptor activity: implications for the pharmacologic management of anxiety disorders


Abstract

Fear, anxiety, and trauma-related disorders, including post-traumatic stress disorder (PTSD), are quite common and debilitating, with an estimated lifetime prevalence of ~28% in Western populations. They are associated with excessive fear reactions, often including an inability to extinguish learned fear, increased avoidance behavior, as well as altered cognition and mood. There is an extensive literature demonstrating the importance of N-methyl-D-aspartate receptor (NMDAR) function in regulating these behaviors. NMDARs require the binding of a co-agonist, D-serine or glycine, at the glycine modulatory site (GMS) to function. D-serine is now garnering attention as the primary NMDAR co-agonist in limbic brain regions implicated in neuropsychiatric disorders. L-serine is synthesized by astrocytes, which is then transported to neurons for conversion to D-serine by serine racemase (SR), a model we term the ‘serine shuttle.’ The neuronally-released D-serine is what regulates NMDAR activity. Our review discusses how the systems that regulate the synaptic availability of D-serine, a critical gatekeeper of NMDAR-dependent activation, could be targeted to improve the pharmacologic management of anxiety-related disorders where the desired outcomes are the facilitation of fear extinction, as well as mood and cognitive enhancement.

 https://www.nature.com/articles/s41398-020-00870-x


Serine compilation research

 https://1drv.ms/w/s!Aqo5695_r4Gr1nGvD7TY2VRR6KX2?e=JQpdUu


Comments

Post a Comment

Popular posts from this blog

Paneth Cells - guardians of the intestinal tract

  Click for the AI slideshow: https://sl.bing.net/hBioK3sTdDw From Google Gemini: Paneth Cells: The Guardians of the Gut Paneth cells are specialized epithelial cells found at the base of the intestinal crypts (small invaginations in the intestinal lining). They play a crucial role in maintaining the gut's health by acting as a first line of defense against harmful microorganisms. Key Functions: Antimicrobial Defense: Paneth cells produce and secrete a variety of antimicrobial peptides and proteins, such as lysozyme, defensins, and phospholipase A2. These substances help to kill bacteria, fungi, and other pathogens that may invade the intestinal tract. Regeneration of Intestinal Epithelium: Paneth cells contribute to the maintenance and regeneration of the intestinal lining by supporting the stem cells located nearby. Immune Regulation: These cells participate in regulating the immune response within the gut, helping to balance the body's reaction to both beneficial and ha...
Post a Comment
Read more

Microbiome SCFAs & AutoImmunity

  Does SCFA impact immune and inflammatory pathways? Show thinking Yes, absolutely! Short-Chain Fatty Acids (SCFAs) are major players in controlling immune and inflammatory pathways, both within the gut and systemically. This is one of the most significant and exciting areas of research on SCFAs. Here's how they exert their control: Interaction with G-Protein Coupled Receptors (GPCRs): GPR41 and GPR43: These are the most well-studied SCFA receptors, found on various cell types throughout the body, including immune cells (e.g., neutrophils, macrophages, T cells), gut epithelial cells, and adipocytes. When SCFAs (particularly acetate, propionate, and butyrate) bind to these receptors, they trigger intracellular signaling pathways that can influence immune cell function, cytokine production, and inflammatory responses. Histone Deacetylase (HDAC) Inhibition: Butyrate (and to a lesser extent propionate) are potent inhibitors of HDACs. HDACs are enzymes that modify histones, proteins aro...
Post a Comment
Read more
You can buy most of this at Kroger's, I listed the pictures below. The idea is that you are targeting the gut, the microbiome to be exact. I am not going to list out all the studies but they have discovered that the right bacteria in the gut can change a lot of things including metabolic, neurological, immune responses, weight gain and many other things.  Increasing the good bacteria such as bifidobacteria etc. can also suppress the bad bacteria which have been linked to numerous problems.  There are products that you can buy on Amazon and these will also support the microbiome by giving the nutrients they need.  Kroger's has the ones in the pictures below, you will find the Cleveland Kraut in the refrigerated section and so is the Kefir. Both of these are live foods meaning they contain the good bacteria. Sauerkraut as canned does not work since there are no live organisms.  You will have to experiment with the doses; I do a couple of tablespoons of the kraut and ju...
Post a Comment
Read more