BRONZE

Using MEG Coherence Based Hallmarks & Protein Modification In a Treatment for Schizophrenia

Focused on Innovating a Novel Treatment Option for Schizophrenia
Yug Oza
Grade 9

Problem

 

Using MEG Coherence Based Hallmarks & Protein Modification In A Treatment for Schizophrenia

A PPTX link to the presentation above: https://drive.google.com/file/d/1ZmsxxfpwskgBLTmlWq6Xw-uVV-ag3Vlj/view?usp=sharing 

Abstract

Schizophrenia is mental disorder the involves breakdown between thought, emotion, and behavior. About 1% of the world is diagnosed with this illness and will be continued to be diagnosed in the future. Individuals have incredible changes in their life such as being disconnected from family and friends to hallucinations and delusions. Schizophrenia is currently the fifth most affectionate mental disorder around the world. The causes for this disorder are many chemical imbalances in the brain of neurotransmitters. This is a wide spreading disorder in the brain and is very severe as it progresses on to its stages and if not treated then negative outcomes are highly likely.

 

Problem 

Schizophrenia is a mental disorder that involves a breakdown between thought, emotion, and behavior. Individuals with this disorder go through drastic changes which lead to symptoms such as hallucinations and delusions. Current treatments can treat Schizophrenia in its initial stages through antipsychotic medications and psychotherapy, but these treatments aren't as effective in the later stages. Having considered this, the question was how key hallmarks of Schizophrenia and proteins could lead to a more effective and efficient treatment for this disorder.   

 

Thesis

Current treatments for Schizophrenia have worked psychologically and are efficient to treat Schizophrenia in the earlier stages of symptoms. Having considered this, the only question was how the worst types of Schizophrenia could be treated more efficiently. If Schizophrenia could be treated using modified proteins and key hallmarks based on surgical principles, then this may result as an efficient treatment for Schizophrenia. Meaning that a Schizophrenic individual would experience less symptoms because there would be less imbalances of neurotransmitter levels in the affected region of the brain. 

 

 

BACKGROUND RESEARCH

 

 

Schizophrenia

Schizophrenia is a mental illness in which chemical imbalances in the brain cause significant changes in thought emotion and behavior.

 

Causes of Schizophrenia

Specific causes of schizophrenia are unknown, but it is known that the imbalance of neurotransmitters and a combination of genetic, psychological, and environmental factors that can cause this disorder.

  • Neurotransmitters
  • Dopamine
  • Serotonin
  • Glutamate
  • Norepinephrine              

Symptoms

Symptoms are primarily based on how severe the disorder is on the individual’s brain and what stage it has progressed to. The symptoms are:

  • Hallucinations
  • Delusions
  • Depression
  • Disorganized/Negative thinking
  • Abnormal behavior
  • Not being able to express certain emotions

Diagnosis

Current diagnostic tests are:

  • Physical examination
  • Oral tests and screenings - this includes MRI and CT scanning
  • Psychiatric Evaluations
  • DCS - diagnostic criteria for schizophrenia

The diagnostic tests will be applied based the type of symptoms the individual is facing. Diagnosis criteria may vary on the type of Schizophrenia symptoms that are showing on the individual.  

 

Current Treatments

Schizophrenia is a condition that can be treated through certain drugs and therapy.

  • Electroconvulsive Therapy:  ECT scans stimulate electric impulses from the individual’s brain while they are in anaesthesia.
  • The types of drugs that are used to treat schizophrenia are antipsychotic, anti-anxiety, and antidepressants.
  • The overdose of these drugs can possibly increase neurotransmitters whereas taking a certain amount can reduce the number of chemical imbalances.

 

 

 

MEG Coherence Based Hallmarks

 

Figure 1 - MEG Coherence (Magentoencepahlogrpahy)

 

The MEG machine detects neuronal and synaptic activity and it will also detect any changes or patterns in the synapses of neurons and neuronal activity itself.

  • Magnetoencephalography machines are used by detecting magnetic fields produced in the brain to make magnetic source images. These magnetic fields are produced by the activity of neurons. MEG machines will measure the neurons in a specific order. This is so there is no interference between position and the signals of the MEG and the neuron.

 

  • The measuring of the neuronal activity can also tell which part of the cortex has high levels of neurotransmitters passing through the synapses of the neurons. MEG machines can also detect CSF movement in the subarachnoid spacing between the skull and brain.

                                 

 

This image shows a magnetoencephalography screening test comparing a brain affected by depression and an average individual's brain. 

 

  • The differences in the color show the absences in connectivity using MEG. The MEG will detect the synaptic transmission and magnetic fields to detect the speed of neurotransmitters passing between the synapses. 
  • MEG machines will detect the magnetic fields due to the synaptic transmission between the neurons.
  • Not all parts that have decreased connectivity can be targeted with treatment, but they can be treated through antipsychotic medication.

 

Figure 2 - Neuroglia ( Hallmark - 1) 

 

  • Neuroglia are cells that protect the neurons and serve different functions. The neuroglial cells can be detected by MEG in the subarachnoid spacing. Neuroglial cells like astrocytes and ependymal cells can be found within the CSF and they play a major role in treating unhealthy and deficient neurons
  • Other neuroglial cells can be found in neural tubes within the spinal cord or the cerebral aqueduct. 

 

Neuroglia is a valid hallmark for Schizophrenia because it serves the function to ultimately protect the neuron. Schizophrenia is an illness in which it involves the overuse of neurotransmitters. The neuroglial cells detect the levels of synaptic transmission by controlling the number of neurotransmitters released at the nerve terminal. Schizophrenia will target glial cells which cause them to lose their ability to control synaptic transmission which leads to the over transmission of neurotransmitters. 

 

                                    

                                                                

  

                                                              

 

Figure 3 - Cerebrospinal Fluid - (Hallmark - 2)

  • Cerebrospinal fluid and Neuroglia can be considered as one of the hallmarks due to CSF containing many different types of Neuroglia. To specifically analyze the neuroglia, it will have to be extracted from the CSF. 

 

  • Chemical analysis on the neuroglia will tell how cells react to the synaptic transmission and if they are serving their proper functions or not.

 

  • The chemical analysis will show how efficient or inefficient they are. Depending on the analysis the neuroglia will be  extracted from the CSF and then transported to the affected region of the brain. 

 

  • Cerebrospinal fluid is produced by the choroid plexus which is in the ventricles. 

 

  • CSF is a type of hallmark/biomarker that can indicate and help diagnose many other diseases like Alzheimer’s Brain tumors                                                              

 

 

 

                                                                             

Cerebrospinal Fluid has many important elements in its composition. CSF contains more different types of protein, than blood plasma. Cerebrospinal fluid also contains certain amounts of potassium, glucose, and calcium but in very little amounts. During the formation of CSF, the choroid plexus also adds growth factors of the CSF like iodine, and vitamins B1 and B12. CSF samples are taken from the thoracic part of the spinal cord which is also known as the spinal tap.  

  

Why These Hallmarks 

These are valid hallmarks of Schizophrenia because they are curial in diagnosing and identifying Schizophrenia. Neuroglia cells are very crucial for the health of neurons and how they function and having considered this these cells would essentially play an essential role in balancing neurotransmitter level in neural network. This is very important because the imbalance of neurotransmitters is what is known to be the leading cause of Schizophrenia and the neuroglia cells can stop this from happening. There are six different neuroglial cells which all play different roles to ensure the health, safety, and proper functioning of the neurons. Cerebrospinal fluid and neuroglia can be considered as one hallmark because cerebrospinal is composed of several different neuroglial cells meaning is just as a valid hallmark as neuroglial because of differences in CSF conditions. The MEG machine is a very important part of  this treatment and this is because it detects the magnetic fields and waves created from synaptic activity in the brain. This is very important because this allows us to determine where there are abnormalities in synaptic activity meaning that those regions of the brain must be targeted. 

 

 

Research on Proteins

Proteins

- The research here focuses on the different types of proteins in the brain and what functions they serve. 

  • Vesicular Glutamate Transporter 1 - (protein)

Neurotransmitter release at excitatory synapses highly depends on the glutamate import into synaptic vesicles by VGLUT1. VGLUT1 and VGLUT3 are two of the three vesicular glutamate transporters and these two are very  common in adult brains.

  • Vesicular inhibitory amino acid transporter - (protein)

This is a protein in humans that is encoded by the SLC32A1 gene and is a specific protein for synaptic vesicles and is responsible for vesicular storage of GABA and glycine. This is key for GABAergic and Glycinergic neurotransmission. 

  • Vesicular Glutamate Transporter 3 - (protein)

A protein that transports glutamate into synaptic vesicles before it is released into synaptic cleft. This is a protein encoded by the SLC17A8 GENE.

  • Sodium dependent phosphate transporter protein 1 - (protein)

This is a protein in humans encoded by the SLC17A1 gene. It is found within the Central Nervous System (CNS).

  • Sialin - (protein) 

Sialin is a protein encoded into human by the SLC17A5 gene. It is stored as sialic acid in the brain and is found throughout the Central Nervous System (CNS).

  • Monocarboxylate transporter - (protein) - (MCT)

 MCT's are membrane proteins which are carriers for lactate, pyruvate, and ketone bodies. There are three different types of MCT in the brain. MCT 1 is known to be within endothelial cells, ependymocytes, and astrocytes. MCT 4 is known to be found in all these cells other than astrocytes. MCT 2 is found in neurons for majority of the time.

  • Ion transporter - (protein)

This protein is known as a transmembrane protein that moves nutrients (ions) across membranes from a high number of particles to a low number of particles.

  • Monoamine neurotransmitter (chemical compound)

They are neuromodulators that have one amino group connected to an aromatic ring through the help of a two-carbon-chain. EX: dopamine and serotonin.

  • Excitatory amino acid transporter 1 - (protein)

Also known as Glutamate Aspartate Transporter 1. This protein is also found in the plasma membrane which give it    the ability to remove glutamate from the extracellular space.  

  • Excitatory amino acid transporter 4 - (protein)

This protein is encoded by the SLC1A6 gene. EAAT4 is found in the cerebellum area of the brain. The protein has high capabilities to have dissimilar chemical species to be capable to form chemical bond. The  Excitatory amino acids can form these bonds which are L-glutamate and L-aspartate

  • Solute carrier family 25 member 22 - (protein)

A protein encoded by the SLC25A22 gene and its responsibilities are to encode mitochondrial glutamate carrier. This protein and the genes associated with this are found in colorectal tumor cells.

 

 

PROTEIN MODIFICATION - POST TRANSLATIONAL MODIFICATION METHODS

  

Phosphorylation

Phosphorylation changes the structural conformation of protein and causes the protein to be activated or enhance its function. De-phosphorylation is when the protein becomes de-activated. In the process of phosphorylation, a phosphoryl/phosphate group is added to the protein (PO3)/(PO4). Phosphate groups can be found in the human DNA, RNA, and adenosine triphosphate (ATP). The human body in general needs phosphate to help repair bones  teeth and help nerves function. 

                                                                                              

                               

Phosphoryl Group:  PO3-2

Phosphate Group:  PO4-2 

 

    • Phosphoryl groups are consisting of phosphorus and oxygen. The process of phosphorylation and de-phosphorylation are carried out by certain enzymes.         

Importance of Phosphorylation

    • Important for glycolysis
    • It is used for protein interaction
    • Protein degradation
    • Enzyme inhibition 
    • Balances homeostasis by regulating energy which is done by chemical reactions.

 

Protein Phosphorylation

    • Happens when the phosphoryl groups are added to an amino acid structure of a protein.
    • Majority of the time the amino acid being used is known as serine.
    • Phosphorylation can also occur on threosine and tyrosine in eukaryotes.
    • Phosphorylation is a type of post translational modification method.
    • Protein phosphorylation is plays an important role in metabolism and spotting pathways. 

Glycolysis

The process where a molecule of glucose is converted into two molecules of pyruvate. Through the help of this process molecules of ATP can be synthesized. 

Protein Degradation

When proteins breakdown into smaller polypeptides or amino acids. 

 

 

Other Post Translational Modification Methods Considered

Glycosylation

A chemical reaction where a carbohydrate (glycosyl donor) is attached to a hydroxyl.

    • Glycosyl Donor:  a mono-carbohydrate that will react with an appropriate glycosyl acceptor in order to form a new glycosidic bond.
    • This glycosyl donor will be attached to a hydroxyl.

 

Glycosyl Donor

              (Glucosyl Bromide)                 +                             Hydroxyl Group

                                 COMBINE                         

 

    • There can be many different types of glycosyl donors glucosyl bromide is known as one of them.   
    • A hydroxyl group which attaches itself to certain molecules that contain a hydrogen atom and oxygen atom.
    • Glycosylated protein is more flexible and suitable for serving their functions 

 

Ubiquitination

Ubiquitination is an enzymatic posttranslational modification in which a ubiquitin protein is added to a substrate protein. The protein ubiquitin is found in all cellular tissues in humans and can also be found in eukaryotic cells and this protein helps with synthesizing new proteins and destroying of bad and negative proteins.

Destruction of Proteins: Ubiquitin Proteasome System (UPS)

In the degradation of proteins ubiquitin is added to the amino group on the  side chain of a lysine residue. Additional proteins of ubiquitin are also added with each other and this forms a multiubiquitin and this process is also known as proteolysis.

 

Lipidation

Lipidation is a process in which the function of the proteins is enhanced through many different types of lipids and these functions can only be augmented by enhancing their binding affinity to biological membranes.

Proteins can be modified by six different types of lipids which are:

    • Fatty acids
    • Isoprenoids
    • Sterols
    • Phospholipids
    • Lipid derived electrophiles (LDE)

 

Protein Modification

These protein modification methods are going to be applied on the specific proteins that will be extracted from the different parts of the nervous.

Proteins

    • Vesicular Glutamate Transporter -1 (VGLUT-1)
    • Vesicular Glutamate Transporter -3 (VGLUT-3)
    • Serotonin Transporter (SERT)
    • Dopamine Transporter (DAT)

Post Translational Modification Applied on Proteins

The most efficient PTM method is phosphorylation and every protein will be phosphorylated to modify it and enhance its functions. The proteins will be modified and will be used alongside neuroglial cells.

 

VGLUT-1/3  -  Vesicular Glutamate Transporter 1/3

The neurotransmitter glutamate is very important in our synaptic activity. To ensure that synaptic efficiency is balanced, the synaptic vesicles are refiled with glutamate by the VGLUT proteins.

In the process of neurotransmission, the synaptic vesicles are retrieved by endocytosis. When the synaptic vesicles are in the position to be refilled again this is all possible depending on the activity of VGLUT proteins. The transport rate of VGLUT increases at the hippocampal glutamatergic terminal. VGLUT-1 and 2 are most found in adult brains (mature brains). This protein is highly associated with membranes of synaptic vesicles.

 When the activity of this protein decreases this allows the brain to be more vulnerable to diseases.

    • The lack of glutamate transmission is what leads to symptoms associate with schizophrenia.

 

                         

 

When the modified VGLUT-1/3 will be transported through the neural pathways, they will eventually make way to the neurons beginning the process again.

 

Phosphorylation on VGLUT-1/3

In basic terms phosphorylation would be the process of adding phosphoryl and phosphate groups to a protein to enhance their functions.

    • VGLUT-1    +    (PO3 -2) or (PO4 -2)

 

Enhancement of Proteins

Since these proteins are associated with the certain neurotransmitters, making them phosphorylated will allow them to prevent over neurotransmission alongside with the neuroglia cells. When the neurotransmission is going to be balanced this will allow neural networks and pathways to function properly.

    • With some proteins a sodium dependent transporter may have to be used for this protein to accomplish its task (reaching the neural networks and assisting the neuroglia cells to balance neurotransmission).

 

 

Serotonin Transporter Protein

The serotonin transporter protein is also known as sodium dependent serotonin transporter. This protein removes serotonin from the synaptic cleft back into the synaptic boutons causing this to stop the functions of serotonin in areas that are not needed. Overall SERT plays a key role in regulating serotonergic neurotransmission and limiting the amount being used. 

 

Phosphorylation on Serotonin Transporter

SERT  +   (PO3-2) or (PO4-2)  

 

 

Exocytosis

A certain process in which a bulk of molecules are released. In this process membrane bound secretory vesicles are carried to the cell membrane and the other remaining molecules would be secreted into the extracellular environment

 


 

 

Dopamine Transporter Protein (DAT)

 

  • The dopamine transporter also known as dopamine active transporter or DAT is a membrane spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cystol. The cystol is the place where other transporters isolate dopamine into vesicles for storage and later release.

 

  • Dopamine controls many functions such as movement, cognition, mood, and the feeling of reward. All of these functions can’t be controlled unless if the DAT manages the amount of use of DAT.

 

  • The dopamine transporter is a target for several different types of narcotics which can also lead to schizophrenic symptoms because some of these narcotics are reason for imbalance in neurotransmitters.

                                                                                              

 

Phosphorylation on Dopamine Transporter

DAT    +     (PO4-2) or (PO3-2)

     

 

 

    

Method

 

The method/procedure was structued knowing the consequences of this treatment. There are eleven steps used in the application of this treatment. Every procedure was carefully analyzed to assure the safety and to understand the pros and cons of this treatment. This treatment procedure can also be implied as secondary treatment on three different neuroglial cancers. 

 

*The procedure created is not meant to be applied by any means until further medical apporval of this idea. This is only a hypothetical treatment design  

 

 

Treatment Procedure - Interbody Cell Transplant -

INTERBODY CELL TRANSPLANT DESIGN - FULL PROCEDURE  OF TREATMENT

 

1. Basic principles of craniotomy will be applied from the point of the brain where the ventricles are located to the embryonic precursor in the spinal cord, and the affected region of the brain. (embryonic precursor neutral tube in the spinal cord where the neuroglial cells are located).

 

2. A Syringe - 8 inches in length will be placed in the subarachnoid space surrounding the brain and the spinal cord. The syringe will take a sample of the CSF. (CSF – Cerebrospinal Fluid) - ( S1 SYRINGE)

 

3. The CSF and the neuroglia within the CSF will be analyzed to examine their behavior if they are healthy or not.

 

4. After knowing where there are differences in synaptic transmission and activity in specific regions of the brain through MEG the S2 syringe will be used.

 

5. The S2 syringe will contain the neuroglial cells and CSF - ( Hallmarks 1 & 2). Which will be transported to the certain affected regions of the brain directly through the incision made in the skull.

 

6. After this step a fMRI scan will scan the whole brain, specifically the affected regions of the brain.

 

7. S3 Shunt connecting from the neural tube and ventricles to the affected part of the brain will transport a greater amount of healthy neuroglial cells than the S1 and S2 Syringe tubes. This shunt will be there from the duration of the surgical process. (This procedure will only be there if needed this depends on how worse the illness has progressed over the brain).

 

8. The modified/phosphorylated proteins – VGULT 1 & 3, SERT, DAT, will be transported directly through opening of the skull which leads to the brain. Prior to this procedure there will be chemical analysis performed on each of the modified proteins. Depending on the individual and the health of their brain additional amount of neuroglia and proteins may have to be transported.

 

9. At last the basic principles of cranial anatomy will end the procedure. Artificial duramater will be used to cover the incision made in the skull and original duramater layer. The titanium screws/plates will be used to attach the drilled piece of the skull back on to the skull.

 

10. The post fMRI scans and MEG scans on the affected part of the brain and the neurons will show that synaptic transmission has been well balanced. This step will be performed at least 48 hours after the procedure has been completed because it will take time for the results to show

 

11. The astrocytes (type of neuroglial cell) will start to take away the remains of the dysfunctional and dead glial cells.  

 

Example of Craniotomy

 

Shunt Tube & Syringe Being Used

  

 

 

The Process of Phosphorylating Proteins

Extraction

    1. Extract DNA sample of the patient
    2. Remove the phosphate/phosphoryl groups
    3. Analyze them and store them.

PHOSPHORYLATION PROCESS

  1. Extract the DAT, SERT, VGLUT-1/3 using the S1 syringe from the central nervous system (CNS)
  2. Under the specific conditions attach the phosphate/phosphoryl groups to the DAT with the necessary equipment and specific testing.  

With these steps simplified steps the necessary proteins will be phosphorylated and healthy to be used. These steps will be used on every protein (DAT, SERT, VGLUT-1/3, NET).

 

MATERIALS USED

  • Most of the materials used in this procedure have either been self designed or are surgical tools used for neurosurgery (craniotomy)

Materials

- MEG machine (magentoencephalogrpahy machine) 

- Neuroglia cells 

- Cerebrospinal Fluid 

- Storage comparments for the proteins and neuroglia cells.

-  Proteins: DAT, NET, SERT, VGLUT-1/3

-  Light Microscopes

- Probes for protein modification 

- fMRI machine ( functional magnetic resonance imaging machine)

- S1 Syringe (self designed) 

- S2 Syringe (self designed) 

- S3 Shunt tube (self designed)  

- Surgical forks, drills, scissors, hooks, and probes

- Artificial duramater 

- Titanium Screws/plates

The materials used here are all the possible tools needed for this procedure. During the duration of this treatment the tools will be used according to the steps of the procedure. 

 

Transportation of Neuroglia Cells and Proteins

  • The neuroglia cells will be transported directly through the incision/opening made in the skull. This is a  very efficient way of transporting the neuroglia cells and the proteins because they come in direct contact with the brain meaning that they will be effective very fast and efficiently. 
  • Another possible way of transporting the proteins and neuroglia is through the blood brain barrier (BBB). The BBB is a very risky but also very efficient option for transportation of the neuroglial cells and the proteins and there are several reasons behind this. 
  • The blood brain barrier serves the function to control nutrients (ions) and cell transfer between the blood and the brain, and vice versa. This is very efficient because the proteins and neuroglia transfer process becomes much easier when they are transported through the BBB. 
  • There is a risk factor when it comes to contacting the blood brain barrier. The risk in contacting the blood brain barrier is that it is very much likely to be disturbed then this will cause the immune cells to meet the neurons causing nerve damage. This can further lead to many other injuries and problems in the brain like MS.  

Analysis

 

Pros & Cons

  • The Interbody Cell/Proteins Transplant treatment for Schizophrenia has no major side effects that could potentially have a major impact on a individual. Materials are the only possible way that there could be any potential harm to the brain or any other nerve tissue and this is a problem that can be avoided. 
  • As far as the concerns for the materials, the syringe/shunt tubes and other neurosurgical tools are very safe to use because this procedure is very minimaly invasive compared to other craniotomies and surgical methods. 

Pros 

  • Schizophrenia. This is a very huge factor to be considered because these hallmarks are crucial in balancing neural connectivity and neurotransmission. 

 

  • The Interbody Cell/Protein Transplant is a very efficient process completed in a very short period. If the steps to this procedure are followed correctly then this treatment can be completed in three hours (180 minutes). 

 

  • Proteins used and modified/phosphorylated were correlated with the specific neurotransmitters involved in cause for the key symptoms for this disorder.

 

  • Considering that there will be two custom designed syringes and shunt tubes used in this process and these tubes are designed to be more efficient than other syringes making these tools very viable and much easier to use.  

 

  • This is a valid treatment option soon and proved that it can potentially have a significant impact on balancing neurotransmission and synaptic activity. 

 

  • ***The Interbody Cell/Protein Transplant  can be possibly used to treat two other types of neuroglial cell cancers. These    neuroglia cell cancers are Oligodendroglioma, Low Grade Astrocytoma. Neuroglia cells that are extracted from different areas of the nervous system are valid and capable of targeting growing malignant and benign cancers and destroying them.
  •  

Cons

  • The Interbody Cell/Protein Transplant does have a few cons to its procedure. The first con being that there can be any sort of infection caused because of the contact between the brain, surgical materials, and other nerve tissue.                          

 

  • During phosphorylation of the proteins they might not be phosphrylated properly which may cause malfunction or problems when they enter the brain. 

 

  • Blood clots may form every any surrounding areas of the brain are damaged which may lead to severe brain problems. 

 

  • When extracting the cerebrospinal fluid there can possibly be a leak which may potentially lead to disorders like hydrocephalus.

 

  • If any neural networks or certain areas of the brain are harmed then this may lead to temporary or permenant or temporary loss of certain functions and abilities. 

 

Assesing the Cons

  • Even though though there are many cons present in this treatment, these cons can only be caused due to basic principles of craniotomy. There are several different options to prevent these situations from occuring.  

 

  • To prevent blood clots from forming there will be basic cotton like material surrounding the area where the incision is going to be made. This will allow the nerve tissue to be protected from the sharp edged of the surgical tools.

 

  • Disruption in phosphorylation is very unlikely to happen, but if it does happen it won't be as serious as long as the protein's functions are stable and able to work.

 

  • The leakage of CSF can be avoided by the S3 shunts tubes because this shunt is used particulary for the CSF flow control towards the affected reigon of the brain

 

 

Neuroplasticity & Schizophrenia

  • Neuroplasticity means the change of neural function and structure over time. It can be beneficial to treat this disorder, or it can also be considered as one of the factors for the growth and progression of this disorder.

 

  • Neuroplasticity can explain many altercations and abnormalities in the brain during imbalance in neurotransmitter levels. When there are chemical imbalances in an individual’s brain, the current growth can identify how the brain has changed throughout the progression of Schizophrenia.

 

  • Even though neuroplasticity being an advantage in understanding chronic mental disorders (CMD), it stops after age 25 and this is due to the brain being fully developed and mature. As neuroplasticity ends, many neural network are lost which eventually may lead to the human brain being more vulnerable to neurological disorders. 

 

  • Neuroplasticity plays a major role in how well this treatment would work on an individual and this is because the growth and developement of the brain will cause differnt change in neurological functioning meaning there will be changes in neural networks. Having considered this the neuroglia and proteins may not have a long lasting impact on controlling neurotransmitter levels.

 

Conclusion

 

Summary -  Brief Description

‚Äč This treatment uses the hallmarks that are very efficient and are key in identifying the research of this project which is  focused around creating an efficient and novel treatment option for Schizophrenia. The main way in which this treatment will be conducted is  through using key hallmarks and modified proteins. Neuroglia cells and cerebrospinal fluid are the two hallmarks that I targeted during research, I was able to figure that both were viable sources that could be used. Having considered that neurotransmission and synaptic activity would need to be balanced by not just the health of the neurons but also many different factors, I decided to target proteins. Targeting proteins was very challenging in terms of understanding their functions, health, and abilities. Knowing that PTM of a protein in the brain can be stopped by imbalance of neurotransmitters, I had to research another way of modifying these proteins. This method was to phosphorylate the proteins through phosphate/phosphoryl groups extracted from the blood and combining them with the proteins. During the process of constructing this treatment, the biggest factor to consider was how it could be designed to be minimally invasive and safe. Acknowledging  this, I designed three syringes and shunt tubes which will certainly make this procedure safe and very efficient. Every step in this procedure was studied and analyzed to assure that the risk level is minimized, and the efficiency is maximized. 

 

Conclusion

Schizophrenia is a growing mental disorder around the world and has very severe and devastating symptoms which is noticed by a breakdown between thought, emotion, and behavior. The most debated question around the world is how there can be a more efficient treatment created for Schizophrenia. My thesis stated that if proteins associated with specific neurotransmitters were to be modified and used alongside key hallmarks of Schizophrenia under craniotomy principles, then a significant balance could be spotted in the neurotransmitter levels and synaptic connectivity. With the highly likely and predicted outcomes, the design of the Interbody Cell/Protein Transplant can show a very accomplished and satisfying result if it is ever clinically applied. Having Considered the pros and cons of the Interbody Cell/Protein Transplant, this novel treatment option can be very beneficial to treat Schizophrenia. Overall, I conclude that this treatment design can have  impact on our society as another option besides the use of anti-psychotic medication and therapeutic drugs, which can have show lasting negative side effects. This reasearch and treatment innovation is to help treat individuals with Schizophrenia, however, it also seeks  raise awareness and provide knowledge of what  impact mental illness can have on individuals.  

 

What's Next ?

In society today, we thrive on excellence, perfection, and idealism, individuals tend to forget about their mental health trying to meet certain expectations. Innovating a hypothetical treatment; The Interbody Cell/Protein Treatment, gives me the encouragement to progress my research work and keep learning. Seeing how devastating it can be to see someone go through such events and experience tough symptoms, I thrive to raise more awareness in society, so we understand how dangerous and severe mental illness and its outcomes are if they are not treated. Soon, I look forward to working with more skilled and experienced individuals with quite more knowledge and presenting my ideas to them. I believe that the ideas of this  innovative creation are a step in the right  direction to discover and learn how to tackle such situations. Overall, the main goal I look forward to achieving is to bring more awareness into our community about what this illness pertains to and creating such innovations which can help others in the future.

Citations

Citations - APA Formatting

To assure the certainty of the sources used here, every source was compared to insure that the information is not false and is trustable. 

 

Background Research & Research for Hallmarks

  • (n.d.). Retrieved from https://www.psychiatry.org/patients-families/schizophrenia/what-is-schizophrenia

 

  • (n.d.). Retrieved from http://schizophrenia.com/szfacts.htm

 

  • Astrocyte Cells General Information and Resources. (n.d.). Retrieved May 14, 2020, from https://www.astrocyte.info/

 

  • Ependymal Cell. (n.d.). Retrieved May 14, 2020, from https://www.sciencedirect.com/topics/medicine-and-dentistry/ependymal-cell

 

  • Pathological Hallmarks of Schizophrenia: Comparison of Genetic Models With Patients and Nongenetic Models. Retrieved from https://academic.oup.com/schizophreniabulletin/article/36/2/301/1902281

 

  • Jaaro-Peled, H., Ayhan, Y., Pletnikov, M. V., & Sawa, A. (2010, March). Review of pathological hallmarks of schizophrenia: comparison of genetic models with patients and nongenetic models. Retrieved from

 

  • https://www.ncbi.nlm.nih.gov/pubmed/19903746

 

  • Kieffer, S. (2018, December 3). Types of Brain Tumor Surgery: Johns Hopkins Comprehensive Brain Tumor Center.

 

  • Retrieved from https://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/brain_tumor/treatment/surgery/

 

  • Neurosurgery Procedures. (n.d.). Retrieved from https://www.nervous-system-diseases.com/neurosurgery-procedures.html

 

  • Radial Glial Cells: Neuron. (n.d.). Retrieved from https://www.cell.com/neuron/fulltext/S0896-6273(05)00348-X

 

  • Schizophrenia. (2020, January 7). Retrieved from https://www.mayoclinic.org/diseases-conditions/schizophrenia/symptoms-causes/syc-2035444

 

  • Schizophrenia. (2020, May 14). Retrieved from https://en.wikipedia.org/wiki/Schizophrenia

 

  • Schizophrenia. (2020, January 7). Retrieved from https://www.mayoclinic.org/diseases-conditions/schizophrenia/diagnosis-treatment/drc-20354449

 

  • Srinivasan, R., Winter, W. R., Ding, J., & Nunez, P. L. (2007, October 15). EEG and MEG coherence: measures of functional connectivity at distinct spatial scales of neocortical dynamics. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/17698205

 

  • Summary of the Cranial Nerves. (n.d.). Retrieved from https://teachmeanatomy.info/head/cranial-nerves/summary/

 

  • The Blood–Brain Barrier. (n.d.). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292164/

 

  • The Editors of Encyclopaedia Britannica. (2018, September 27). Cerebrospinal fluid. Retrieved May 14, 2020, from https://www.britannica.com/science/cerebrospinal-fluid

 

  • The Ventricles of the Brain. (n.d.). Retrieved from https://teachmeanatomy.info/neuroanatomy/vessels/ventricles/

 

  • Treatment. (2014, August 17). Retrieved from https://www.hydroassoc.org/treatment

 

 

  • Yokota, Y., Eom, T.-Y., Stanco, A., Kim, W.-Y., Rao, S., Snider, W. D., & Anton, E. S. (2010, December). Cdc42 and Gsk3

 

  • modulate the dynamics of radial glial growth, inter-radial glial interactions and polarity in the developing cerebral cortex. Retrieved May 14, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976289/

 

  • Does the brain awaken via a continuous phase transition? (2019, May 23). Retrieved from https://physicsworld.com/a/does-the-brain-awaken-via-a-continuous-phase-transition/

 

  • Elekta. (n.d.). Canada Access Request. Retrieved from https://www.elekta.com/meta/canadaAccessRequest?ref=/diagnostic-solutions/

 

  • staff, S. X. (2018, July 11). Why are neuron axons long and spindly? Study shows they're optimizing signaling efficiency. Retrieved from https://medicalxpress.com/news/2018-07-neuron-axons-spindly-theyre-optimizing.html
  • Ventricles of the Brain flashcards on Tinycards. (n.d.). Retrieved from https://tinycards.duolingo.com/decks/8ozCAm2f/ventricles-of-the-brain      

 

 

Bibliography for Proteins 

  • Dopamine transporter. (2021, January 03). Retrieved from https://en.wikipedia.org/wiki/Dopamine_transporter#:~:text=The dopamine transporter (also dopamine,for storage and later release.

 

  • Zhang FX;Ge SN;Dong YL;Shi J;Feng YP;Li Y;Li YQ;Li JL;. (n.d.). Vesicular glutamate transporter isoforms: The essential players in the somatosensory systems. Retrieved from https://pubmed.ncbi.nlm.nih.gov/30273635/ 

 

  • Norepinephrine. (n.d.). Retrieved from https://www.britannica.com/science/norepinephrine 

 

  • Serotonin Transporter. (n.d.). Retrieved from https://www.sciencedirect.com/topics/neuroscience/serotonin-transporter 

 

  • SLC20A1. (2020, December 31). Retrieved from https://en.wikipedia.org/wiki/SLC20A1 

 

  • UniProt ConsortiumEuropean Bioinformatics InstituteProtein Information ResourceSIB Swiss Institute of Bioinformatics.

 

  • (2021, February 10). Retrieved March 14, 2021, from https://www.uniprot.org/uniprot/Q9NRA2 

 

  • (2020, November 10). Retrieved March 14, 2021, from https://en.wikipedia.org/wiki/Monocarboxylate_transporter

 

  • Ion transporter. (2021, March 04). Retrieved from https://en.wikipedia.org/wiki/Ion_transporter#:~:text=From Wikipedia, the free encyclopedia,homeostasis, energy production, etc

 

  • Schlessinger, A., Geier, E., Fan, H., Irwin, J. J., Shoichet, B. K., Giacomini, K. M., & Sali, A. (2011, September 20). Structure-based discovery of prescription drugs that interact with the norepinephrine transporter, NET. Retrieved from https://www.pnas.org/content/108/38/15810#:~:text=The norepinephrine or noradrenaline transporter,neurons (2, 3). 

 

  • Urea transporter. (2021, January 30). Retrieved from https://en.wikipedia.org/wiki/Urea_transporter#:~:text=A urea transporter is a,-A and UT-B.&text=Their inhibition results in diuresis,collecting ducts of the kidney. 

 

  • Lin, Z., Canales, J. J., Björgvinsson, T., Thomsen, M., Qu, H., Liu, Q., . . . Caine, S. B. (2011). Monoamine transporters: Vulnerable and vital doorkeepers. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321928/#:~:text=Monoamine transporters are transmembrane proteins,) (1, 2). 

 

  • Excitatory amino acid transporter 1. (2021, January 14). Retrieved from https://en.wikipedia.org/wiki/Excitatory_amino_acid_transporter_1  

 

  • Magi, S., Piccirillo, S., Amoroso, S., & Lariccia, V. (2019, November 13). Excitatory Amino Acid Transporters (EAATs): Glutamate Transport and Beyond. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888595/ 

 

  • Solute carrier family 25 member 22. (2020, October 11). Retrieved from https://en.wikipedia.org/wiki/Solute_carrier_family_25_member_22

 

  • Calcium-binding mitochondrial carrier protein Aralar1. (2020, December 05). Retrieved from https://en.wikipedia.org/wiki/Calcium-binding_mitochondrial_carrier_protein_Aralar1

                                                                                                                                         

Bibliography – Protein Modification Methods  

  • Post-transcriptional modification. (2020, December 05). Retrieved from https://en.wikipedia.org/wiki/Post-transcriptional_modification 

 

  • Overview of Post-Translational Modification: Thermo Fisher Scientific - US. (n.d.). Retrieved from https://www.thermofisher.com/ca/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/overview-post-translational-modification.html 

 

  • Home - PMC - NCBI. (n.d.). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/ 

 

  • Methylation. (2021, January 25). Retrieved from https://en.wikipedia.org/wiki/Methylation#:~:text=In the chemical sciences% 

 

  • Drazic, A., Myklebust, L. M., Ree, R., & Arnesen, T. (2016, June 11). The world of protein acetylation. Retrieved from https://www.sciencedirect.com/science/article/pii/S1570963916301169 

 

  • Arey, B. J. (2012, September 26). The Role of Glycosylation in Receptor Signaling. Retrieved from https://www.intechopen.com/books/glycosylation/the-role-of-glycosylation-in-receptor-signaling 

 

  • William C. Shiel Jr., M. (2018, December 21). Definition of Ubiquitination. Retrieved from https://www.medicinenet.com/ubiquitination/definition.htm 

 

Bibliogrpahy for Images

  • (n.d.). Retrieved from https://www.bioinformatics.org/tutorial/1-3.html 

 

  • (n.d.). Retrieved from https://www.google.com/search?q=types of neuroglia&safe=strict&rlz=1C1GGRV_enCA766CA766&sxsrf=ALeKk02JoZUr-kBb8U_Yxrm_FgYIVWKlKg:1615860258085&source=lnms&tbm=isch&biw=1422&bih=680#imgrc=qcZpQ1j2UnnLCM 

 

  • The Brain 101. (2019, November 01). Retrieved from https://www.brainhq.com/brain-resources/cool-brain-facts-myths/brain-101/ 

 

  • Carboxylic acid. (2021, March 08). Retrieved from https://en.wikipedia.org/wiki/Carboxylic_acid 

 

  • McHugh, P. C., & Buckley, D. A. (2015, February 14). The Structure and Function of the Dopamine Transporter and its Role in CNS Diseases. Retrieved from https://www.sciencedirect.com/science/article/pii/S0083672914000223 

 

  • Phosphoryl group. (2020, October 24). Retrieved from https://en.wikipedia.org/wiki/Phosphoryl_group

 

  • 5a: Functional groups - Honors Chemistry Online. (n.d.). Retrieved from https://sites.google.com/site/honorschemistryonline/6-organic-chemistry/5-functional-groups 

 

  • Bailey, R. (n.d.). Ventricles of the Brain. Retrieved from https://www.thoughtco.com/ventricular-system-of-the-brain-3901496 

 

  • Adult Central Nervous System Tumors Treatment (PDQ®)–Patient Version. (n.d.). Retrieved from https://www.cancer.gov/types/brain/patient/adult-brain-treatment-pdq 

 

  • Anne. (n.d.). Leinwandbild Gehirn-Scan, X-ray • Pixers® - Wir leben, um zu verändern. Retrieved from https://pixers.de/leinwandbilder/gehirn-scan-x-ray-50992349 

 

  • Serotonin Transporter. (n.d.). Retrieved from https://www.sciencedirect.com/topics/neuroscience/serotonin-transporter

 

 

 

 

 

 

 

 

Acknowledgement

Acknowledgement 

During the research of my project I was inspired and supported through many different ways. Something that strongly inpsired me to do this project was a book by Johaan Hari, "Lost Connections", this book  delves into the severe impacts of mental health specifically regarding, the impact of  antipsychotics on the health of individuals. In this book there are several important topics on the  right and wrong types of treatments for mental health ilnesses and this is really important because antipsychotic medications have long lasting negative side effects. When doing my background research I was motivated to pursue this idea due to the lack of knowledge  indivudals have on mental health and its' treatments. With the support and encouragment of my parents and teachers I was able to pursue my idea and build up on my research.