2024-08-01

The Variabilities of Dopamine (₯) - PART II: CL: 0000700

CellsAtWork:dopaminergic neuron (DAN, CL: 0000700)
 
Hi everyone, I’m Dopamine Girl. As an organic compound, I am what chemist ChEBI calls 18243. My relationship with you humans can start from the Cell Ontology ID number 0000700 defined by biologists. The working cell is a dopaminergic neuron (DAN, CL: 0000700), a neuron (cell) that uses dopamine as the neurotransmitter. Without further ado, let’s look at Figure 1 to understand DAN’s work characteristics and knowledge genealogy.

Learn about cells and dopamine from the Cell Ontology (CL), mainly because the cell knowledge described by CL is pretty mature and complete (20 years ago from 2004), covering cell types from prokaryotes to mammals, though not including plants cell. The rich diversity of CL can be seen from that it has imported 17 external ontologies and been reused by 86 external ontologies. CL is also widely used, such as the Human Cell Atlas (the Human Cell Atlas) established in 2016 by an international research alliance composed of more than 3,000 biologists, informatics scientists, and clinicians from 99 countries, and the Human Cell Atlas of the National Institutes of Health in the United States. The HuBMAP project uses CL as its core resource as well.

Fig 1: DAN in the Cell Ontology.

In the Variabilities of Dopamine (₯) - PART I:ChEBI:18243, we introduced the father-child relationship in ontology, which is the up-and-down relationship of the knowledge structure or the "depth" of the ontology. In fact, the expression of depth in CL can be as deep as 31 levels, which is the 31 generations of the family tree in vernacular. Figure 1 shows the direct upper layer of DAN is the neuron that releases catecholamines as neurotransmitters - catecholaminergic neurons, namely the father of DAN. They inherit some characteristics of the three major cell families of neural, secretory and electrically activities, and therefore help us to easily grasp the characteristics of DAN as a working cell that releases and secretes dopamine.

Second, we are generally familiar with DAN, which resides in the midbrain, so DAN here is the target tissue for the major neurodegenerative pathologies when it comes to Parkinson's disease. DAN has two lower subcategories in the CL description, among which the midbrain dopaminergic neurons are the children of DAN. Since DAN will degenerate or decrease with age or disease, etc., if the brain cannot produce enough dopamine, the work responsible for transmitting messages cannot be performed normally, which may easily lead to the deterioration of body movements, cognitive sensory emotions, or hormones, as well as mediation and other related diseases.

Another neuron that lives in the inner nuclear layer of the retina, the so-called dopamanergic interplexiform cell, is also a child of DAN. It is not common in the general introduction of dopamine, and related research is relatively little. His specialty is the use of dopamine to regulate nerves in the retina to adapt to light. If he cannot use enough dopamine, it may also cause visual impairment in Parkinson's patients.

Nevertheless, compared to DAN's father-son relationship, siblings of DAN (left-right relationship) are more complicated. The CL ontology describes more than 2,700 cell types, including 660 types of nerve cells and more than 540 types of neurons. Fortunately, we have another body gang to rescue. The U.S. National Library of Medicine's Medical Subject Headings (MeSH) is 70 years old (published since 1954). From the Figure 2, you can learn about the working cell DAN in the nervous and cellular system from the MeSH knowledge tree, and the overview of its neuron cell siblings.

Fig 2: DAN in the MeSH tree

In the ontology, the relationship between father, son, brother and sister is the basic "blood relationship", and another relationship including the description of external knowledge is also the solid power of the ontology. Just like writing a biography, after the three generations of ancestors and grandchildren have been explained, the highlight is to narrate the protagonist's experience and meaningful events. For example, the chemical entity ChEBI:18243 introduced before has simple inclusion, similarity and application relationships. In the second part, our protagonist is a living cellular entity - dopaminergic neuron (DAN), so "biological process" becomes an indispensable element for interpreting knowledge. Through the external gene knowledge ontology (GO) imported into CL ontology, we can further understand the daily working status of biological processes of cellular DAN (Figure 3)

Working cells DAN are neurons that release dopamine through synapses. According to the definition of synapse by the GO ontology: the connection between the axon of one neuron and the dendrite, muscle fiber or glial cell of another neuron.

    Fig 3: DAN, dopamine & synapse base on GO ontology
  • The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell.
  •  As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane.
  • In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.

The biological process of DAN (CL: 0000700) described by the cooperation of CL and GO ontology is shown in Figure 4. Its "relationship" or a grammatical metaphor for the relationship in the knowledge ontology is a verb:

  • has participant
  • has end location
  • results in acquisition of features of

The entities (metaphorically represented as nouns) involved in biological processes are:

  • Fig 4: DAN involved in biological processes, based on CL& GO ontologies　
    synaptic transmission, dopaminergic: The vesicular release of dopamine. from a presynapse, across a chemical synapse, the subsequent activation of dopamine receptors at the postsynapse of a target cell (neuron, muscle, or secretory cell) and the effects of this activation on the postsynaptic membrane potential and ionic composition of the postsynaptic cytosol. This process encompasses both spontaneous and evoked release of neurotransmitter and all parts of synaptic vesicle exocytosis. Evoked transmission starts with the arrival of an action potential at the presynapse.
  • dopaminergic neuron differentiation: The process in which a neuroblast acquires the specialized structural and functional features of a dopaminergic neuron, a neuron that secretes dopamine.
  • astrocyte-dopaminergic neuron signaling: Cell-cell signaling that mediates the transfer of information from an astrocyte to a dopaminergic neuron.

After learning some basic knowledge structure of dopamine as a chemical and working cells DAN, think about it again. If dopamine is multi-variable, then when DAN living in the midbrain releases dopamine, its impact on biology should undoubtedly be the same. Variable, and so on, what unexpected scientific commotion will dopaminergic neurons bring us then? (to be continued)

 

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