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Caenorhabditis elegans, a model animal for studying the regulation of serotonin in the brain

2021-07-13
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With the continuous improvement of biological science and technology, the current models constructed using model organisms are playing an increasingly important role in drug screening. Most transgenic technologies are applicable in mice but much more difficult in other mammals. Other vertebrates (zebrafish) and invertebrates (Drosophila, Caenorhabditis elegans) are increasingly used for drug screening. Patients with depression and anxiety often have lower levels of 5-hydroxytryptamine, and drugs that increase 5-hydroxytryptamine levels are often used clinically in these patients.

What is a 5-Hydroxytryptamine(5-HT)

5-Hydroxytryptamine, also known as serotonin, is an important neurotransmitter in the human body that regulates mood and emotion.  It is also a local hormone and is important in platelet function. However, neuroscientists do not know much about how neurotransmitters affect brain circuits and collective behavior in the complex human brain. New research has recently identified Cryptobacterium hidradenum, which has only 302 neurons, as a powerful system for studying how 5-hydroxytryptamine regulates brain states.

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Where is the 5-Hydroxytryptamine(5-HT)located

The highest concentrations of 5-HT are found in three organs:

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In the wall of the intestine. Over 90% of the total amount in the body is present in the enterochromaffin cells.These cells are derived from the neural crest and resemble those of the adrenal medulla. They are found mainly in the stomach and small intestine interspersed with mucosal cells. Some 5-HT also occurs in nerve cells of the myenteric plexus, where it functions as an excitatory neurotransmitter.

In blood. Platelets contain high concentrations of 5-HT.They accumulate it from the plasma by an active transport system and release it from cytoplasmic granules when they aggregate (hence the high concentration of 5-HT in serum from clotted blood.

In the CNS. 5-HT is a transmitter in the CNS and is present in high concentrations in localised regions of the midbrain

What are the Actions and functions of 5-HT

1.Increased gastrointestinal motility

2.Contraction of other smooth muscle ,bronchi, uterus,for example.

3.Mixture of vascular constriction and dilatation

4.Platelet aggregation

5.Stimulation of peripheral nociceptive nerve endings

6.Excitation/inhibition of central nervous system neurons.

7.In periphery: peristalsis, vomiting, platelet aggregation and haemostasis, inflammation, sensitisation of nociceptors and microvascular control

8.In central nervous system: many postulated functions, including control of appetite, sleep, mood, hallucinations, stereotyped behaviour, pain perception and vomiting.

9.Clinical conditions associated with disturbed 5-hydroxytryptamine (5-HT), including:migraine, carcinoid syndrome, pulmonary

10.Hypertension, mood disorders and anxiety.

The anatomical structure of the nervous system of Caenorhabditis elegans is relatively simple, with only 302 nerve cells, but it contains numerous neurotransmitters similar to the brains of higher animals, such as acetylcholine, dopamine, 5-hydroxytryptamine,  glutamate, and γ-aminobutyric acid and neuropeptides, and is capable of sensing various environmental stimuli and making a variety of responses.

In recent years, the use of model animals as in vivo drug screening models has played an increasingly important role in new drug screening. Caenorhabditis elegans has been used in drug screening due to its simple and complete nervous system, special physiological structure and easy modeling. For example, in the development of drugs for the nervous system, Dalian Chemical of my country has built a high-throughput drug screening platform based on nematodes as a model and combined with microfluidic chips for the screening of anti-neuronal degeneration drugs represented by Parkinson’s disease.

In the long-term practice of searching for drugs, people have established a large number of various drug screening models for new drug screening. Currently, the most commonly used drug screening models are established at the level of tissues and organs, cell and subcellular levels, and molecular and enzyme target levels. Medicilon has established relatively mature drug screening models in the research fields of anti-tumor, immune diseases, anti-inflammatory, cardiovascular diseases, analgesia, and diabetes, including new high-throughput primary screening models that are small, fast, and highly automated , Including in-depth screening of all levels of re-screening models, forming an efficient, multi-level new drug screening platform.

According to online reports, Steven Flavell, a researcher from the Massachusetts Institute of Technology, said that although Caenorhabditis elegans is small, transparent, and has only 302 neurons in the nervous system, it is a study of serotonin’s regulation of brain state. Powerful model animal.

Once in 2018, researcher Flavell’s laboratory published an article in the Cell magazine, revealing how neurons called NSM sensed and sent signals to other neurons through serotonin when C. elegans began to feed bacteria. , Thereby slowing the speed of nematode feeding; since then, researchers have begun to study how to manipulate the serotonin release pattern of NSM to affect the slow behavior of nematodes, and at the same time, researchers have begun to clarify which serotonin receptors are on neurons It plays a key role in the effect, such as observing what changes will happen to the nematode body by genetically knocking out a single receptor or multiple receptors.

Caenorhabditis elegans and mammals have the same basic molecular mechanism that can release and receive serotonin. But unlike mammals, all neurons and connections of Caenorhabditis elegans can be precisely located, and scientists can also exert powerful genetic control on each of its cells, including the expression of five different serotonin receptors in the worm. In addition, the researchers also developed an innovative imaging system that can image the calcium ion activity in each neuron in real time. Even under experimental operating conditions, the nematodes can slide and move freely. Twist.

Essentially, Flavell’s team can almost completely control the nematode’s serotonergic system (serotonergic system, SS), and at the same time observe the true reflection of every neuron in its entire brain, which may give the nematode a certain degree The ability (which mammals do not have) to figure out how different modes of serotonin release stimulate different receptors on neurons, thereby regulating different body behaviors. Researcher Flavell said that by using the defined serotonin functional paradigm and advanced imaging technology, researchers can analyze how the release of serotonin activates different types of receptors through the entire circuit, thereby changing the large-scale activity pattern that produces behavior. .

At present, Caenorhabditis elegans has become the new favorite of developmental biology, neurobiology, and gene function research. Using Caenorhabditis elegans as a model organism has made many achievements in the nervous system, which has greatly promoted the development of life science and technology.

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