Fascinating Aspects of Glycobiology—Part 9 (Brain Development)

Larry A. Law

The brain is the command center for human operations. These operations can be voluntary or involuntary. The sugar, sialic acid (Sia) is one of the eight glycobology sugars of particular interest in brain development. It is often noted as poly sialic acid (polySia or PSA) in the scientific literature. PSA if very often the terminal (last) sugar on cell receptors in the brain. It is the most common sugar in the brain and actively influences connections and brain development.  

Building the Growing Brain in the Young

Brain development in infants is complex, but occurs quickly. By the time a child is two years old, their brain is 80% of its adult weight. Children are born with a complete number of neurons (brain cells), but the synaptic connections between them constantly route and re-route themselves after birth. These roads between brain cells become the neural pathways sustaining our ability to think, learn, make associations, and remember. Neurons do not connect directly to other neurons. There is a synaptic gap or space between the end of one neural highway and another. Electrical signals coming down to the end of one highway cause chemical neurotransmitters to be generated. These neurotransmitters are released and diffuse across the synaptic space and bind to receptors on the other highway's synapse; this procedure results in an electrical charge being generated on that side. This is how we make connections. Sialic acid plays a dominant role in proper brain development and cognition. It is vitally important for children to have an adequate supply of this sugar nutrient throughout this developmental period to facilitate the proper construction of the pathways in their brains. 

PolySia is a Major Regulator

Within the developing fetus, PSA serves a critical role in building the emerging nervous system. PSA Neural Cell Adhesion Molecules (PSA-NCAM) increase neural plasticity which means brain cells can more easily break and form synaptic junctions. PSA-NCAM direct construction of the new roadways and guides them to travel through the growing brain to the proper destination (brain cell) to establish a new synaptic connection. Synapses represent the street intersections within a city. The roads are the pathways electrical signals can travel. At intersections, they can cause signals to be sent down side roads and/or stimulate other pathways. This is how a random smell can generate an associated memory of another event that occurred years ago.

​Each neuron can connect with over 40,000 synapses. There are 10,000 specific types of neurons. The brain processes information at 268 miles per hour (432 km/hr) and during pregnancy 250,000 neurons are created every minute. One quadrillion (1000 trillion) synapses are created before a three-year old begins to trim away half of them. The brain eliminates the roads built which are no longer needed. Roads that carry a lot of traffic become interstates and major highways in the brain. Local roads are useful too, but some roads are seldom or never used. They end up as dirt paths and the brain trims these away and eliminates them from the city's traffic map. A brain cell (neuron) with its axon pathways extending to other neurons is depicted below. 

Importance of Sialic Acid

PSA expresses itself in more than 90 different Sia residues/varieties. Sia is attached to glycoproteins and glycolipids and is often the terminal sugar on the chain. When it is not created properly, psychiatric disorders like schizophrenia, autism, depression, and bipolar disorder result. Human brain cells have two to four times more Sia than other cell glycocalyxes in the human body. Sia enables neurotrasmissions between neurons and impacts learning and memory. Studies on piglets (their brains resemble human brain's structure and function more closely than almost any other animal) demonstrated that a diet rich in Sia vastly improved their cognitive function. 

The Brain's Lymphatic System

Some people view science as a static thing. They cite a fact as if it is the last word on the subject. They don't realize that science is always evolving and changing. It is not dogma. A great example occurred in 2015. Researchers discovered that the brain is supported by the lymphatic system. The lymph system exists throughout the brain, but no one recognized it for what it was until 9 years ago. For decades, the medical system believed and taught that the lymphatic system existed only below the head. This unexpected discovery had huge ramifications. It means that the brain is not a sterile environment. There are microbes (friendly bacteria) that lodge in our brains. The brain has its own microbiome just like the gut does. The interplay between brain neurons, glial cells, and bacteria are all related and work together for optimal brain function. 

Sugar nutrients play a key role in this new view of the brain. Sugars like mannose operate in the same manner as gas in the gas tank of macrophages (immune system cells). A well-functioning immune system requires activated macrophages. They carry beneficial microbes to the brain to support the microbiome there. They stimulate the immune system to fight unwelcome bacteria. The balance between good and bad bacteria is vital in the gut and in the brain. Elimination of waste and toxins out of the brain via the lymph is crucial because the brain is housed in a fixed bone cavity that cannot expand. Blockages in the lymph system can cause fluid build-up resulting in swelling and inflammation in the brain, initiating disease. The bottom line is that these glycobiology sugars stimulate our immune system defense cells. They provide the building blocks necessary to build cell-surface, sugar structures enabling the brain and the body to perform correctly. They are vital nutrients for brain health.