The Killing Cures - Cues for Chemical Imbalance: Parkinson's Disease
Medicine is essential to the lives of many. It is taken with a person everywhere they go. Shouldn't society gain a better understanding of whether or not the item at the top of the priorities list effectively accomadates those needs? Parkinson's is the second most common neurodegenerative disease behind Alzeimers. The current treatment method of Levodopa and Carbidopa was only chosen because it was thought that when we lose something, it must be renewed. In most cases however, when an attempt is made to add lost neurotransmitters, it is done as if one shovels the snow in their front yard whilst a heavy snowfall takes place. Is this ideal? Is it effective? If not, what other factors should be given deep consideration? As for the main driving question which gives this entire project its objective: Could the development of Parkinson's disease occur due to underlying mechanisms linked with those of depression and do the current treatment methods accomodate such mechanisms within the systems?
It has already been confirmed that the current treatment methods for Parkinson's disease are mainly used for the purpose of easing symptoms. Therefore different approaches were taken to keep the results for the objective of this project to be valid and suitable. Knowing through background research of the limited efficacy of antideppressant treatment on deppression patients [severe deppression], underlying mechanisms of chemical imbalance were thoroughly taken into account. This effort was essential in maintainin progress to meet the objective of the overall study, in which certain mechanisms were put into consideration for the purpose of bringing forth potential hypotheses. Current theories on causes for Parkinson's disease were also taken into thorough account and represented within the study to prove the underlying mehcanisms that aren't accomodated through the current treatment methods.
Key terms for obtaining information based on the underlying mehcanisms of both Parkinson's disease and severe depression:
Glutamate toxicity, oxidative stress, ROS, α-synuclein, astrocytes, microglia, nitric oxide, lewy body, oligomer, peroxyitrite, cytokines, calcium influx, EAAT2, GLT-1.
Criteria set for approaches in obtainin information based on underlying mechanisms and current treatment methods for both Parkinson's disease and severe depression:
- Information was obtained from highly credited sources and/or texts
- Source included keyterms
- Diverse choice of source type for information accumulation [internet, books, knowledgeble people]
Keyterms used for obtaining information based on current treatment methods of Parkinson's disease and severe depression:
Levodopa, cabidopa, entacapone, AAAD, DDCI, DBS, parkinson's, symptoms, dopamine, dyskinesia.
The Nervous System
- A highly complex network of nerve cells which transmits nerve impulses throughout the body.
- Made of two systems:
- Central Nervous System [CNS]: Includes the brain and spinal cord.
- Peripheral Nervous System [PNS]: Includes the nerves that branch off of the brain and spinal cord.
- Consists of three main functions:
- Sensory input: The information collected by sensory receptors.
- Integration: When the nervous system processes the input and decides what to do.
- Motor Output: The occuring response once the nervous system activates a certain part of the body.
Types of Glial Cells
- The most abundant cell type in the CNS, glial cells, surround, support, and provide insulation for neurons.
- Glial cells in the CNS:
- Astrocytes: synaptic support, controls blood flow, and governs material exchange.
- Microglia: source of immune defense against invading microorganisms.
- Ependymal cells: line cavities in the CNS, create and circulate cerebrospinal fluid.
- Oligodendrocytes: creates an insulating barrier around axons [myelin sheath].
- Glial cells in PNS:
- Satellite cells: surround, support, and regulate nutrients among neurons.
- Schwann cells: create an insulating barrier around axons [myelin sheath].
- Membrane potential is the difference in electrical charge between the outside and inside of a neuron.
- Grouping of ions allows a difference in electrical charge.
- Inside of neuron at rest includes:
- Positively charged potassium ions [K+]
- Negatively charged proteins [larger than K+ ions]
- Outside of neuron at rest includes:
- Positively charged sodium ions [Na+]
- Resting membrane potential is -70 mv
- Na+/K+ pump: A protein creating a gradient between sodium and potassium
The Action Potential
- A flow of an electrical current down an axon due to depolarization.
- Stimulus occurs:
- Sodium enters cell: slightly increases membrane potential.
- Reaches -55 mv.
- Depolarization: several voltage gated channels open.
- Membrane potential becomes positive 30-40 mv.
- Electric current flows down neuron, towards its axon terminal.
- Membrane potential reaches the peak: K leaves cell.
- Hyperpolarization: Refractory period.
- Repolarization: Na+K pump controls ion flow for polarization.
- An electrical or chemical signal using an action potential from the presynaptic neuron to fuse excitatory and inhibitory neurotransmitters towards the postsynaptic neuron, firing an action potential through its dendrites.
- Action potential [presynaptic neuron] reaches axon terminal:
- Voltage gated calcium channels open.
- Calcium mobilizes vesicles filled with neurotransmitter particles.
- Neurotransmitters fuse into synaptic cleft.
- Neurotransmitters bind to receptors on postsynaptic neuron.
- Reuptake: neurotransmitters are reabsorbed by presynaptic neuron.
- Chemical messengers which play a role in transmitting signals from the presynaptic neuron to the postsynaptic neuron through a chemical synapse.
- Affects physical and psychological functions.
- Play a major role in neurotransmission by communicating within the neural field, controlling our usual and occasional actions.
- Over sixty distinct types of neurotransmitters have been identified.
- May be influenced by drugs or diseases to malfunction or to cure physical and psychological disorders.
- Also called 5-hydroxytryptamine [5-ht] and functions as an inhibitory neurotransmitter that is categorized as a monoamine.
- Located in the brain and spinal cord [CNS] in the field of the nervous system as it is also found in the intestines and the cells of platelets.
- It is distinguished from the other neurotransmitters in its monoamine category due to it being derived from the amino acid, tryptophan, unlike the catecholamines of the other monoamines, dopamine, epinephrine, and norepinephrine.
- Tryptophan undergoes a process of hydroxylation for the addition of the a hydroxyl group [OH] making 5-hydroxytryptophan [5-HTP].
- 5-hydroxytryptophan then undergoes decarboxylation in which aromatic amino acid decarboxylase catalyses a carboxyl group from 5-HTP, producing serotonin.
- Primarily located in the raphe nuclei of the brain stem.
- Serotonin is very well known for regulating mood, particularly the feeling of well-being and happiness although, its functions reach further.
- Balanced levels of serotonin allow states of happiness, calmness, focus, reduction of anxiousness, and being emotionally stable overall.
- Like any other neurotransmitter, imbalanced amounts of serotonin can cause issues, but imbalances of serotonin in particular are linked to many psychological disorders that are mainly related to mood.
- Functions as an excitatory or inhibitory neurotransmitter which is also known as hydroxytyramine that also falls into the monoamine category.
- Out of the monomines, dopamine is also a catecholamine which a catechol group.
- Dopamine and serotonin are commonly perceived as having the same psychological effects, although they don’t. While they are both similar, they have their distinguishing traits. Serotonin targets regulation of mood whereas dopamine carries out the feeling of pleasure from a pleasurable experience.
- Releases of dopamine occur from these pleasurable experiences to signal that something important is taking place and that is must be remembered. Not only does such action allow pleasure to be felt but dopamine then plays a role in memory in order to remember an experience as such.
- Neurons containing dopamine are also involved in emotional responses and some aspects of movement as it regulates contraction within skeletal muscles.
- Commonly known as adrenaline while it serves as an excitatory neurotransmitter and a hormone.
- Produced and secreted in the medulla oblongata of the central nervous system and the medulla of the adrenal glands.
- The process of it undergoing its release starts off with a strong emotion as a stimulus in which the amygdala triggers the hypothalamus to activate the autonomic nervous system [a control system that regulates bodily functions].
- As part of the autonomic nervous system, the medulla of the adrenal glands are stimulated to release epinephrine into the bloodstream. Secretion of epinephrine then causes increases heart rate, blood pressure, and increased muscle strength.
- Also known as noradrenaline which serves as a hormone and an excitatory neurotransmitter.
- Norepinephrine acts as a stress hormone in particular and is released into the bloodstream due to a stressful event, similarly to epinephrine [adrenaline].
- While it activates energy and alertness, norepinephrine is also secreted from the medulla of the adrenal glands, like epinephrine. As the two share several similarities, they have their distinguishing characteristics.
- Since these two neurotransmitters are both triggered by strong emotions such as stress, they are likely to have similar effects when released including increased heart rate, raised blood sugar levels, or physical changes towards blood vessels.
- While epinephrine has a slightly more of an effect towards the heart, norepinephrine plays a role in the narrowing of blood vessels, enabling an increase in blood pressure.
- An organic chemical that serves several critical functions as an overall excitatory neurotransmitter while the contrary when in the heart.
- May be found in all motor neurons as a stimulator for the contracting of muscles as it plays a major role in regulating such action in the somatic nervous system within the PNS.
- While serving as an excitatory neurotransmitter in the neuromuscular junctions [chemical synapses between motor neurons and muscle fibers], it acts directly to open ligand-gated channels which allow cations into muscle fibers for contraction.
- When serving as an inhibitory neurotransmitter, acetylcholine targets its effects towards the heart. Parasympathetic nerves of cranial nerve X innervate synapses at cardiac muscle cells where acetylcholine will bind to M2 muscarinic receptors to slow down heartbeat.
- Overall, Acetylcholine has a major role in muscle contraction, arousal, short-term memory, and learning.
- Serves as the central nervous systems main excitatory neurotransmitter.
- While at balanced concentrations, this amino acid is crucial for brain functions including learning and memory.
- Three ionotropic glutamate receptors were identified which are NMDA, AMPA, and kainate receptors. When activated with the binding of glutamate, each allow sodium ions to pass through membranes which is what gives glutamate its main reputation as an excitatory neurotransmitter.
- Activation of NMDA and AMPA receptors may result is synaptic plasticity, the strengthening or weakening of a synapse by long-term potentiation or long-term depression, which affect learning and memory.
Gamma Aminobutyric Acid [GABA]
- Referred to as an amino acid neurotransmitter for its structure of an amino acid and its served function of an inhibitory neurotransmitter.
- GABA serves its inhibitory function as it binds to it GABAa and GABAb receptors. When binded to GABAa receptors which are ionotropic receptors permeable to Cl-, it will hyperpolarize membrane potential, decreasing chances for an action potential fired.
- When serving its function toward the GABAb receptors, it will cause K+ channels to open, allowing K+ to flow out of the neuron and hyperpolarizing the membrane potential, decreasing chances for an action potential to fire.
- GABA prevents nerve impulses from being travelled too quickly which in turn prevents symptoms of being overwhelmed or anxiety.
Classifying Neurotransmitters by Function
- Neurotransmitters determine whether or not an action potential will be fired in the postsynaptic neuron due to the function of each.
- Excitatory neurotransmitters: Neurotransmitters that bind to ligand gated channels on the postsynaptic membrane and open them to start depolarizing the neuron, starting an action potential:
- Acetylcholine [may depend on type of receptor attached to]
- Dopamine [may depend on type of receptor attached to -- excitatory or inhibitory]
- While some neurotransmitters trigger an action potential from the postsynaptic membrane, others may prevent it which are categorized as inhibitory neurotransmitters.
- Inhibitory Neurotransmitters: Unlike excitatory neurotransmitters, inhibitory neurotransmitters prevent an action potential and don’t trigger depolarization in the postsynaptic membrane:
- Gamma-aminobutyric acid [GABA]
Neurotransmitters - Amino Acids
- Amino Acids: Organic molecules composed of an amino group [-NH2], an acidic carboxyl group [-COOH], and an R group which is unique for each type of amino acid.
- Gamma-aminobutyric acid
Neurotransmitters - Monoamines
- Depending on a neurotransmitters type, it could be categorized by monoamines, amino acids, and peptides.
- Monoamines: Neurotransmitters containing an amino group which is also connected to an aromatic ring by a two-carbon chain:
- Epinephrine [hormone + neurotransmitter]
Neurotransmitters - Peptides
- Peptides are chains of amino acids held by peptide bonds which may start out as dipeptides [two amino acids linked together]. Peptides may act as hormones or neurotransmitters such as the following:
Influence on Neurotransmitters & Leading Effects
- Majority of negative influence on neurotransmitter leading to malfunction are caused by one’s actions such as experiencing stress through an event of some sort or consuming bad influences such as the following:
- Cocaine: Such a drug targets the neurotransmitter dopamine but may also affect norepinephrine and serotonin. When these neurotransmitters are released from the presynaptic neuron and bind to receptors of the postsynaptic neuron, cocaine blocks the reuptake of the neurotransmitters. This allows the neurotransmitter concentration within the synaptic cleft to increase and the natural effect of the neurotransmitters is amplified on that postsynaptic neuron.
- Leading Effects:
- Target towards dopamine: increased dependence [dopamine regulates addiction for pleasure]
- Target towards serotonin: increased feeling of confidence [serotonin regulates self esteem]
- Target towards norepinephrine: increased energy [NE regulates fight or flight response]
- Alcohol: While targeting receptors for GABA, serotonin, acetylcholine, and NMDA receptors for glutamate, alcohol inhibits neurons by an extraordinary amount. Such destruction occurs through the binding of alcohol on receptors to keep them open longer for more negatively charged ions to pass through. This may harshly affect glutamates excitatory effect on the NMDA receptors. Overall, alcohol reduces neuron activity.
- Leading Effects: poor memory and slowed reflexes.
- Nicotine: A target towards acetylcholine as it binds to the nicotinic receptor. For addiction of nicotine, it stimulates cholinergic pathways which determine the releasing of dopamine [dopamine regulates addiction through pleasure]. When binding onto a nicotinic receptor, nicotine, desensitizes it for a prolonged period of time [in chronic smokers] and so no neurotransmitter may have an effect on the receptor in that time period.
- Leading Effects: Due to nicotine enforcing dopamine release, it may be continued to be consumed, targeting effects towards the heart and desensitization yet it stills activates functions of acetylcholine.
- An occurrence of an imbalanced amount of certain neurotransmitters while there is either too much or too little of them.
- Chemical imbalance is associated with the cause of mental illnesses although, other factors may play a role in one’s cause of suffering from a mental illness. Chemical imbalance does serve as a reason for psychological disorders such as depression or schizophrenia but it may not be the initial reason for such things to occur.
- This is referred to as the “Chemical Imbalance Theory”.
- Due to no evidence of why the chemical imbalance takes place at first, researchers of the medical field put other factors of what patients experience into consideration such as symptoms of a certain condition.
- Medication to treat psychological disorders that were thought to be entirely caused by chemical imbalances were created in 1970s. Patients with these disorders are still prescribed with these medications which are called antidepressants.
- Many antidepressants are SSRIs [Selective Serotonin Reuptake Inhibitors] or SNRIs [Serotonin-Norepinephrine Reuptake Inhibitors].
- Antidepressants have a success of rate of about 50% which is pointed out by researchers of the medical field as evidence that chemical imbalance isn’t the initial cause of the following mental illnesses:
- Major Depression
Chronic Stress = Chemical Imbalance
- While experiencing stressful events, action will take place starting with the secretion of epinephrine and norepinephrine from the adrenal glands. This will initiate the fight or flight response as these neurotransmitters activate their function in response to stressful events such as increased heart rate and contracted muscles.
- A hormone called cortisol which is also released from the adrenal gland and helps fuel the fight or flight response in stressful situations as it regulates several bodily functions:
- Regulation of blood pressure
- Increases blood sugar
- Controls inflammation
- After a stressful event dies down, cortisol levels fall in order to maintain the body’s resting state earlier although it may take time for ones calm side to be retrieved.
- In response to a stressful event, cortisol is released by the following steps:
- A stressful event must first be identified once the amygdala senses a threat, Stimulating the hypothalamus to release corticotropin-releasing hormone [CRH].
- CRH signals the pituitary gland to secrete adrenocorticotropic hormone [ACTH].
- ACTH travels down to the adrenal glands causing release of the stress hormone, cortisol.
- Cortisol then takes action in response of the previous steps from stress by making temporal changes to deal with a situation by:
- Stimulating gluconeogenesis in the liver to increase glucose levels.
- Constricting blood vessels, increasing blood pressure which diverts oxygen to muscles for strength to take action during the fight or flight response.
- When chronic stress is experienced, cortisol levels increase, causing several issues including chemical imbalance through the steps below:
- High levels of cortisol stimulate the release of the hormone, glucocorticoid which then induces release of high glutamate levels.
- Glutamate toxicity takes place in which high levels of glutamate are released and while several are then able to bind to non-NMDA receptors, triggering an electrical charge strong enough to remove the Mg ion out of pathway through the NMDA receptor, calcium will enter the cell.
- Overtime, an increase in the sensitivity of NMDA receptors for glutamate will develop.
- As NMDA receptors become overactivated, high levels of Ca+ will enter the postsynaptic neuron.
- With prolonged activation of excitatory synaptic transmission, these high calcium levels result in activation of molecules that are capable of causing cell death by rupturing them.
- Such actions result in the damaging of receptor sites for the neurotransmitters, serotonin and dopamine. Therefore, release of these chemicals are decreased, reducing the amount of them, causing a chemical imbalance.
Treatment for Chemical Imbalance
- While antidepressants may have been effective in some cases, they continue to only have an overall 50% chance of curing mental illnesses. These medications also serve as a temporary help and chances of suffering from the same condition later on are likely occur. Like most medications, antidepressants have their side effects.
- While antidepressants mainly focus on the damage done in this case, a chemical imbalance, it would best to find the route cause/source of the issue and stop it from there or find the main changes to what triggers chemical imbalance.
- In most cases, high concentrations of cortisol, leading to glutamate toxicity trigger chemical imbalance and it would be best to begin with this root cause.
- The glucocorticoid steroid hormone, 11-deoxycortisol undergoes a process by which the steroid hydroxylase, 11-beta hydroxylase converts this hormone into cortisol.
- The medication Metyrapone, inhibits 11-beta hydroxylase, preventing the conversion of 11-deoxycortisol, inhibiting the secretion of cortisol.
- While putting an end to the damage reached to neurons by lowering the concentration of cortisol with this medication, working with the remaining neurons that aren’t damaged would then be saved from being ruptured.
- Using antidepressants after treatments with metyrapone would be more effective than without metyrapone due to the fact that without lowering high concentrations of cortisol, dopaminergic and serotonergic neurons would continue to be ruptured through glutamate toxicity. Therefore, use of antidepressants with high levels of cortisol would continue to damage neurons, not allowing the full use of antidepressants to be taken into action.
- While using medications with several side effects aren’t easy to cope with and may lead to risk of receiving the same psychological disorder later on such as antidepressants would be looked down upon, there are natural alternatives to the curing of such disorders.
- While exercise, sleep, and healthy eating are nodded upon and forgotten by several people, they tend to play a crucial role in maintaining neurotransmitter concentrations.
- Neurodegenerative [2nd most common behind Alzheimer's] -- progressive
- Usually occurs among the elderly population, age 60+
- First Symptoms:
- Decline in motor function
- Major motor problems:
- Slow movement
- Issues with balance, more likely to fall
- Death of dopaminergic neurons within substantia nigra
- Substantia Nigra: Midbrain, basal ganglia, two sides on brainstem -- SN pars compacta [SNpc] and SN pars reticulata [SNpr], dopaminergic neurons mainly compacted in SNpc
- Dopaminergic neurons of SN project to striatum, pathway: nigrostriatal dopamine pathway: facilitates movement
Current Treatment Methods for Parkinson’s
- Replace lost dopamin: L-dopa → precursor of dopamine
- L-dopa crosses the blood brain barrier due to enzymes recognizing it as a typical amino acid
- Converted to dopamine by the enzyme aromatic amino acid decarboxylase [AAAD]
- Majority of L-dopa lost in bloodstream due to presence of AAAD in blood stream
- L-dopa/Carbidopa: Carbidopa taken with L-dopa → prevents early breakdown of L-dopa
- Anticholinergics → acetylcholine = opposition of dopamine: less dopamine = ACh effects ↑
- Attempts to bring balance between dopamine and acetylcholine
- Deep brain stimulation [DBS]: surgical procedure delivering electric impulses in certain targets in attempt to disrupt abnormal activity causing motor dysfunctions.
- Targets → subthalamic nucleus, globus pallidus internus, and ventral intermediate nucleus of the thalamus [chosen target depends on decision made by doctor based on symptoms.
- Typical candidates of DBS include patients that have had PD for at least 4 years and improve to an extent from medications yet continue to experience motor complications.
Glutamate Toxicity Link
- Necrosis, Apoptosis
- High influx of Ca²+ increase activity of the enzyme, nitric oxide synthase [NOS]: convert arginine to citrulline → Nitric oxide [NO] produced in process
- NO = free radical → unpaired electron = highly reactive [oxidant -- can cause oxidative stress]
- Oxidative stress = increase in reactive oxygen species [ROS] which damage lipids, proteins, and DNA. ROS = reactive molecules and free radicals formed by the acceptance of oxygen.
- The mitochondria contains a large source of superoxide anions [O²–] as it is essential to the production of adenosine triphosphate [ATP]
- NO is diffused into mitochondria, reacts with O²– = Peroxynitrite [ONOO-] → irreversible inhibition or damage of mitochondrial respiration through oxidative reactions [ONOO- isn’t stable] + DNA damage
- Overall inhibition of mitochondrial respiration = depletion of ATP = cell death
- Xc- system is a 1:1 ratio between cystine uptake and glutamate release mainly occurring within astrocytes. Extracellular glutamate due to excitotoxicity inhibits cystine uptake = inhibition of antioxidant glutathione [cystine = one of the precursors of glutathione]
Glutamate Toxicity Link 
- α-synuclein → protein encoded by SNCA, found in presynaptic terminals, known to be involved in neuroplasticity and neurotransmission
- Misfolded α-synuclein can later form into oligomers [repeated units] or long structured fibrils → degradation systems disrupted
- Imbalance: synthesis vs degradation = Lewy body formation
- Microglia phagocytose α-synuclein → produce cytokines [cell signaling proteins] and ROS
- Microglia respond to damage-associated molecular patterns [DAMPs] → production of ROS
- Dysfunction astroglial transporters such as EAAT2 and GLT-1 [contribute to the reuptake of glutamate] → astrocyte dysfunction = inhibition of glutamate uptake
- α-synuclein secreted by neuron taken by astrocytes for degradation. → α-synuclein concentrations reach a certain threshold at toxic amounts = high accumulation within astrocytes =dysregulation of other astrocytic function → inhibition of glutamate uptake
Depression - Link - Parkinson's
- Early symptom of Parkinson’s disease → increase precaution when depression is diagnosed
- Chemical Imbalance → root cause similar to that of Parkinson’s disease: Glutamate Toxicity
- Parkinson’s treatment made to accommodate symptoms, not the disease itself
- If glutamate toxicity leads to depression, it can gradually lead to Parkinson’s as well
- 50% of PD patients also suffer from depression
Efficacy of Levodopa/Carbidopa/Entacapone Treatment
This data chart provides the amount of patients [%] that experience side effects as a result of Levodopa/DDCI and entacapone intake [Carbidopa is mainly used as a Dopa Decarboxylase Inhibitor [DDCI]. Considering that about 30% of patients experience dyskinesia brings a reasonable amount of concern over the treatment method. However, there isn't much humanity has built up to in order to accomodate the situation in which Parkinson's disease is very difficult to treat considering limited options for treatments due to a lack of relitively complete understanding of the disease and how it can be treated. On a positive view, this data table explicitly debunks the myth that all patients treated with levodopa develop dyskinesia.
This graph compares the effectivty of levodopa/carbidopa/entacapone vs. levodopa/carbidopa for improving quality of life of Parkinson's disease patients. One aware of the fact that entacapone is used to ensure that more of levodopa is being brought into the brain/preventing early breakdown, similar to carbidopa except used as an adjunct, they can easily connect the pieces between that and the mean changes in the graph. levodopa/carbidopa/entacapone clearly has a much better ouput in which several areas of quality of life have improved for patients of Parkinson's disease [relative to before taking the medication whilst experiencing the symptoms]. On the other hand, levodopa/carbidopa alone shows fewer improvements and worsening in the categories within quality of life. However, Q7 leans more towards a physical symptom based questionaire which is typically focused on in the treatment of Parkinson's disease and both bars appear to be reletively closer in quantity yet levodopa/carbidopa/entacapone still has a slightly better performance. [Note: this is data taken from patients at the twelvth week of treatment.
This graph compares a three dose drug intake over the course of 450 minutes to the plasma levodopa level in the brain [ng/mL]. It is clear that the levodopa/carbidopa/entacapone troughs are relatively higher than those of levodopa/carbidpa alone, therefore representing a higher plasma levodopa level which would allow for more of the levodopa to be present past the plasma, giving off its effect to relieve symptoms. This ultimately proves the relative efficacy of levodopa/carbidopa/entacapone.
One cannot always look at the explicit view of the cube, not to mention that it already has several sides to it, however even thorough analysis of each side isn't enough. One must also look at what connects the sides and make logical assiumptions and hypotheses. Therefore we find ouselves with the analysis of the different sides in which the facade over the chemical imbalance theory which covered the fact that several mechanisms come into play before the chemical imbalance stage to drive a neurological disorder like depression into place. Such underlying mechanisms playing large roles in the development of severe depression also appeared in the path leading to Parkinson's disease. This included glutamate toxicity being the main mechanism to ultimately contribute to death of neurons through apoptosis. Its role drove smaller systems such as oxidative stress, astrocyte dysfuntion due to the high accumulation of α-synuclein causes dysregulation of other astrocytic functions such as glutamate uptake, cystine uptake for the production of the antioxidant glutathione, along with other processes which can directly lead to cell death. The objective of this project, deciphering whether or not current treatment methods of Parkinson's disease and severe depression effectively accomodate any underlying mechanisms, has been met. Therefore, it is clear that greater precautions should be taken as soon as depression is diagnosed, consisting of treatment which directly stops the source rather than the damage the source has caused whilst the dangerous activity of the root cause takes place such as glutamate toxicity, attentuation of the amygdala, and inhibition of cortisol secretion. Hopefully such information can raise awareness of the matter allowing for improvements in the treatment for those suffering from Parkinson's disease and severe depression.
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- Parents: First introduced me to the topic of "neurotransmitters" when being told about how certain emotions can relate to activity within the brain
- Teachers: Encouraging figures who ensured that I continued to learn and pursue my interest of the field of neruoscience and psychology in a usefull manner
- Peers: Engaged in conversations on topics of neuroscience and psychology that I open up, allowing me to actively work with others, maintaining my interest in the matter