Glial Cell Types, Addiction, Optogenetics and Chemogenetics and Beta Amyloid and TAU

Student number: …………………………………….
Neuropharmacology Coursework 2
Date
Question 1: Answer
Glial cells (also called glia) are non-neural cells within the central nervous system and the peripheral nervous system in which electrical impulses are not produced. The central nervous system consists of the brain and the spinal cord, highlighting key locations where these cells are found. Glial cells play different roles. For instance, some have the primary function of providing physical support for the brain, while others provide nutrients to the neurons or regulate the brain's extracellular fluid. There are three types of glial cells in a mature central nervous system: astrocytes, oligodendrocytes, and microglial cells, with each having a specific role. For instance, astrocytes' role is to maintain an ideal chemical environment for neuronal signaling. At the same time, oligodendrocytes provide a lipid-rich layer (myelin) around some axons to speed up the conduction of action potential (1).
On the other hand, multiple sclerosis (MS) is a chronic condition affecting the brain and the spinal cord (2). The condition occurs when the body's immune system attacks the myelin sheath and nerve fibers. The attack by the immune systems leads to inflammation, in which nerve cell processes and myelin are destroyed, resulting in the alteration of electrical signals in the brain. The common symptoms of the disease include fatigue, tingling, weakness, blurred vision, loss of vision, double vision, numbness. Some specific glial cells have significant and specific roles in the pathology of multiple sclerosis.
In recent years, research is increasingly establishing that astrocytes contribute to the MS lesions development. Initially, they were considered to play a role late in MS development by forming a scar post-inflammatory stage (2). However, they are now considered active players in the pathology of the lesion. They are known to secrete various substances, including anti-inflammatory and pro-inflammatory ones. During MS development, astrocytes attract immune cells, damaging a nerve and the area around the active lesion. They result in a lesion scar, which is essential in preventing damage from spreading and acts to prevent the repair of damaged neural.
The role of oligodendrocytes (during normal brain function), as already mentioned, is to assemble myelin (1). Myelin is a multi-layered sheath of membraned wrapped spirally around axonal segments. The purpose of the layer is to hasten the propagation of saltatory impulse. Another function of oligodendrocytes is to support metabolism in myelinated axons, especially during high-frequency spikes in axons (7). During multiple sclerosis, oligodendrocytes are damaged, leading to the loss of myelin in a process called demyelination. Never cells that undergo this process become dysfunctional. Recent research indicates that the earliest pathological event of MS is oligodendrocytes, apoptosis; a combination of rapid demyelination and intense localized microglial activation where peripheral immune cell infiltration is absent (3).
Further, in a normal brain function, the role of microglia is to act as immune cells of the central nervous system. They, therefore, play a crucial role in brain inflammation and infections (8). These cells are highly dynamic, constantly moving to an active survey of the brain parenchyma. They respond rapidly to pathological insults by actively inducing various effects that influence pathogenesis and neuronal protection. However, the role of the cells in a healthy brain is different from their role in an infected brain (3). As already mentioned, part of MS is the demyelination of the myelin. The role of microglia in this aspect is to trigger and implement remyelination, the process through which the myelin is regenerated. The process occurs either simultaneously with or following demyelination. Further, the interaction between microglia and T cells plays a crucial role in MS pathogenesis.
Given the different roles and function each of the glial cells plays in regular brain activity and during infection to the central nervous system, their reaction is an essential part of management treatment (2). For instance, it has been established that astrocytes result in a scar that prevents repair, while microglia are responsible for myelin regeneration. These differing interactions form a crucial aspect of treatment considerations. Thus, these cells are promising targets for the disease-altering treatment of MS. They are essential targets for regenerative therapies to reverse the disease (4). For instance, therapies that suppress the formation of scars by astrocytes are essential because they allow microglia to implement myelin regeneration. Where astrocytes are not suppressed, emerging scars prevent regeneration leading to long-term dysfunction of nerves (1). For instance, drugs like Statin inhibit but do not block microglia, which is critical in lowering microglial activity to boost the immune system against MS without destroying it.

Question 2: ANSWER
Addiction is one of the leading crises of the modern world in connection with drugs and medicine. Addiction to banned drugs such as marijuana, heroin, and cocaine, is often the most discussed in the public domain. However, another form of addiction is that people become dependent on prescribed drugs to sustain their daily functional abilities. Some studies around addiction have concluded that it is a brain disorder (5). In other words, addiction is a chronic relapsing disease that results from a prolonged effect of a drug on the brain. It, therefore, has a behavioral and social-context aspect that forms parts of the disorder. In the study of addiction and the conclusion that it is a disorder of the brain, several theories have been proposed to explain the manifestation of addiction as a disorder of the brain. These include Incentive Sensitization Theory (IST) and the Habit Formation Theory (HFT). Both HFT and IST strive to describe brain circuitry, pathology, and pharmacology.
Under IST, scholars argue that drug addiction is the excessive amplification of the psychological wanting due to triggers, such as cues, without necessarily the amplification of liking (6). Under this theory, two different brain circuits: mediates the psychological process of wanting and mediates liking. Thus, the brain mechanisms that determine the extent to which a reward is 'wanted' can be dissociated from the mechanism that determines the extent to which the reward is liked. In this case, 'Wanting' is a particular form of desire, the mesolimbic incentive salience. This wanting is often triggered in pulses by reward-related cues (6). These cues act as urges to obtain and consume the rewards they provide. According to research, the 'wanting' desire is mediated by the brain's mesocorticolimbic systems involving dopamine control. The intensity of triggered urges depends on factors like length of use, the current state of the dopamine-related brain system, and the extent to which the brain wants the cue's reward (6). This interaction causes 'wanting' peaks to be amplified and manifested by rain states that enhance dopamine reactivity. These states include stress, intoxication, appetites, and emotional excitement.
In other words, this theory supports the argument that addiction is a disorder of the brain because prolonged use of addictive substances alters how the brain functions. This is why recovery therapies involve the slow reversal of the addiction process to allow the brain to begin generally functioning without reliance on the said drug or substance. Potentially addictive substances produce long-lasting changes in the brain organization, leading to this disorder. The incentive motivation and reward systems are examples of the systems that are altered to lead to the disorder in which the brain reward systems become hypersensitive to the substance and the associated stimuli.
Similarly, the Habit Formation Theory (HFT) posits that regular repetition of activity results in a habit that develops into a behavior (9). A habit becomes behavior when an individual begins to experience mental or physical health problems and daily functioning. For instance, in the case of addictive substances, habit begins by using an illicit drug or prescribed medicine for a given logical reason. In the former, for instance, the user can cause a moment of 'highness,' while in the latter, the purpose could be to control pain from a chronic illness through prescribed painkillers. However, the use becomes a habit because the repetition alters the brain's circuity system of motivation and rewards. The effect is that whenever the habit is missed, the person suffers from withdrawal symptoms that affect their normal functioning. As a result, it becomes behavior and part of the persons' identity for as long as the addiction is inherent (9). The theory supports the statement that addiction is a disorder of the brain because the brain function has been altered to depend on the drugs for normal functioning. Without the habit, a person is bound to face anxiety, stress, and other symptoms that may have long-term consequences on the brain function.
A pharmacological approach that considers habit formation and an essential aspect of addiction look into how the habits can be reversed. In essence, to stop addiction, therapies that identify and contextualize habits are used to improve the reaction of patients to particular cues. Therefore, progressive and sustained habits change plays a significant role in ending addictions.
Therefore, IST and HFT are similar in that they both support the argument that addiction is a brain disorder. Both theories agree that prolonged use of drugs alters brain function and activity. Hence, the alteration of the brain function and activity is the disorder in question in both theories.