The Process Of Novel Coronavirus Invading The Brain Through The Olfactory Nervous System And Leading To Brain Inflammation
Studies have shown that patients infected with COVID-19 can trigger inflammation of the olfactory bulb or even atrophy of the olfactory bulb if the virus further invades epithelial cells in the olfactory bulb, such as capillary epithelial cells, which disrupts the transmission of electrical signals between olfactory neuron cells and mitral neuron cells. Based on the above studies, we can deduce the process of how novel coronavirus invades the brain through the olfactory nervous system.
The following figure shows how the novel coronavirus invades the brain through the olfactory nervous system and leads to brain inflammation:
(1) Novel coronavirus enters through the respiratory tract and attaches to epithelial cells of the upper respiratory tract and lungs. The novel coronavirus recognizes host receptors via the spike glycoprotein (S protein) of coronavirus.
(2) It then binds to ACE2 (angiotensin-converting enzyme 2) receptor and TMPRSS2 (transmembrane serine protease 2) receptor and enters Sertoli cells of the olfactory epithelium and horizontal base cells of the olfactory epithelium in a membrane-fused manner.
(3) Extracellular vesicles (EV) are nanoscale membrane vesicles composed of lipid bilayers and secreted by all cell types. They act as carriers, protecting macromolecules such as proteins and RNAs from enzymatic degradation, and transporting these macromolecules between different cells, from adjacent cells to more distant cells, or immune cells. In addition, specific extracellular vesicles (EVs) have been shown to be able to cross the brain barrier.
(4) Very small amounts of novel coronavirus in Sertoli cells of the olfactory epithelium and horizontal base cells of the olfactory epithelium may be encapsulated into extracellular vesicles (EVs) and then enter olfactory neuronal cells.
(5) In neuronal cells, Dynein protein is the motor protein responsible for retrograde transport of substances from the cilia end to the axons end. The novel coronavirus is likely to be pulled from the cilia end of olfactory neurons to the axonal end by the Dynein protein, thereby entering the olfactory bulb.
(6) In the olfactory bulb, olfactory neurons and mitral neurons communicate neuroelectrical signals through touch process connections, at which time novel coronavirus may be encapsulated into extracellular vesicles (EVs) and then into mitral neuron cells.
(7) In mitral neurons, novel coronavirus may be retrogradely transported by Dynein protein into deeper brain neurons and thus enter the central nervous system of the brain.
The brain region connecting the olfactory bulb is called the limbic system of the brain, also known as the olfactory brain. If the virus further invades the olfactory brain, which is the part of the limbic system of the brain that is responsible for the processing of logic operations for the encoding and decoding of olfactory electrical signals, this makes the electrical signals of the olfactory nervous system unable to be normally understood and operated by the brain, which is the cause of cognitive dysfunction and also one of the causes of brain fog symptoms.
