Week 3.3: The role of neuroinflammation in affective disorders Flashcards
Is the body’s protective response to injury or infection.
Inflammation
It helps the body heal itself after an injury, defend against foreign invaders like viruses and bacteria, and repair damaged tissue.
Inflammation
What is the link between inflammation and the immune response?
Inflammation is part of the immune response. When the body detects a threat, it releases inflammatory molecules called cytokines.
Are small proteins released by cells, particularly those in the immune system, that have a specific effect on the interactions and communications between cells.
Cytokines
Can be pro-inflammatory (promoting inflammation) or anti-inflammatory (reducing inflammation), and their balance is crucial for maintaining health and responding to disease.
Cytokines
A type of cytokines involved in the defense against viral infections and in the regulation of the immune system.
Interferons (IFNs)
Are released as emergency signals to recruit immune cells, hormones, and nutrients to the injury site.
Cytokines
Blood cells that release clotting proteins to stop bleeding at the injury site.
Platelets
These cells release factors that cause vasodilation and vascular constriction to control blood flow to the area.
Mast Cells
A type of white blood cell that is one of the first immune cells to arrive at a site of infection.
They kill and digest pathogens through a process called phagocytosis.
Neutrophils
Another type of white blood cell that secretes cytokines to attract more immune cells and activate tissue repair processes.
Macrophages
Large white blood cells that engulf and digest pathogens and dead cells.
Macrophages
The process by which cells (like neutrophils) engulf and digest pathogens and debris.
Phagocytosis
The widening of blood vessels to increase blood flow.
Vasodilation
The narrowing of blood vessels to reduce blood flow.
Vascular Constriction
Microorganisms such as bacteria, viruses, fungi, or parasites that can cause disease.
Pathogens
The liquid component of blood that carries cells and proteins throughout the body.
Blood Plasma
Are produced anew for each injury or infection, ensuring a tailored and effective immune response each time.
Cytokines
What is the difference between acute and chronic inflammation?
Acute inflammation is a short-term response that is beneficial for dealing with immediate threats. However, if inflammation becomes chronic, it can lead to tissue damage and contribute to various diseases
What are the characteristics of inflammation?
1) Redness
2) Warmth
3) Swelling (Edema)
4) Pain
5) Loss of Function (Immobility)
These are caused by vasodilation. This increases blood flow to the affected area, particularly in peripheral parts of the body like the skin.
Redness and Warmth
This is due to vascular permeability, which allows plasma fluids to accumulate outside the blood vessels. This fluid buildup leads to the swelling observed in inflamed areas.
Swelling (Edema)
Results from the distortion of tissues caused by edema and the pressure of fluids on nerve endings.
Additionally, certain chemical mediators of inflammation, such as bradykinin, serotonin, and prostaglandins, also induce pain.
Pain
This can result from pain that inhibits movement or from severe swelling that physically prevents movement in the affected area.
This was noted by the German pathologist Rudolf Virchow in the 19th century.
Loss of Function (Immobility)
The circulation of blood in the smallest blood vessels, including capillaries, arterioles, and venules.
Microcirculation
The ability of blood vessel walls to allow the flow of small molecules or cells into and out of the blood vessel.
Vascular Permeability
A neurotransmitter that contributes to feelings of well-being and happiness. It also plays a role in the body’s inflammatory response.
Serotonin
A peptide that causes blood vessels to dilate (enlarge), and therefore causes blood pressure to fall. It also increases vascular permeability and is involved in the pain response.
Bradykinin
A group of lipids made at sites of tissue damage or infection that are involved in dealing with injury and illness.
They control processes such as inflammation, blood flow, and the formation of blood clots.
Prostaglandins
Is the body’s immediate response to injury or infection, involving the innate immune system.
This response is usually quick and resolves shortly after the threat is eliminated.
Acute Inflammation
Occurs when the acute inflammatory response does not resolve and persists over a longer period.
This response is delayed and can last from weeks to months to years.
If severe and prolonged, chronic inflammation can lead to tissue damage.
Chronic Inflammation
A type of white blood cell that can differentiate into macrophages and dendritic cells to respond to infection.
Monocytes
Cells that produce collagen and other fibers, playing a crucial role in wound healing.
Fibroblasts
A type of white blood cell involved in the adaptive immune response, including T cells and B cells.
Lymphocytes
Cells that develop from B lymphocytes and produce antibodies to fight infections.
Plasma Cells
It is synthesized from cholesterol and has widespread effects on the body.
Cortisol
Are the final product of the
HPA axis.
Glucocorticoids/Cortisol
What are the roles of glucocorticoids?
Manage and adapt to stress.
Restores and maintains balance in the body during stress.
Modulate neuroendocrine and immune responses
Regulate energy metabolism and inflammatory reactions
Influence cardiovascular function
To exert their effects, they must bind to glucocorticoid receptors (GR)
Glucocorticoids
Are specialized proteins that assist other proteins in folding correctly, preventing misfolding and aggregation.
They help newly synthesized proteins achieve their functional shapes and assist in refolding damaged proteins
Chaperone Proteins
A group of proteins that help other proteins fold correctly and stabilize them.
This complex includes heat-shock proteins, which are produced in response to stress.
Multimeric Complex of Chaperone Proteins
A type of chaperone protein that helps protect cells from stress by ensuring proteins maintain their proper shape and function.
Heat-Shock Proteins
A change in the shape of a protein that can affect its function.
Conformational Change
Moves from one part of the cell to another.
Translocate
The process of increasing or decreasing the expression of specific genes.
Up or Down Regulation
The part of the cell that contains genetic material (DNA) and controls many cellular activities.
Nucleus
Resides in the cytoplasm with chaperone proteins.
Unactivated GR
Effective response depends on the number, affinity, and function of GRs.
GR Sensitivity
What are the GR Sensitivity Factors?
Number of Receptors: The quantity of GRs available to bind glucocorticoids.
Affinity: How strongly the GRs bind to glucocorticoids.
Function: The ability of GRs to bind the ligand (glucocorticoid), translocate to the nucleus, and interact with other signaling pathways.
The process of copying a segment of DNA into RNA, which is the first step in gene expression.
Transcription
The process by which glucocorticoid receptors (GR) increase the transcription rate of a target gene, leading to higher gene expression.
Transactivation
The process by which GR suppresses the activity of other transcription factors, leading to a decrease in gene expression.
Transrepression
Reducing the activity or efficiency of the immune system.
Immunosuppression
Reducing inflammation or swelling in the body.
Anti-Inflammatory
How does the GR help the body?
Reducing inflammation through transrepression.
Increasing protein production when needed through transactivation.
Leads to higher levels of cortisol.
This is observed in conditions like major depressive disorder, schizophrenia, and Alzheimer’s disease.
Hyperactive HPA Axis
Leads to lower levels of cortisol.
This is seen in conditions like post-traumatic stress disorder (PTSD), chronic fatigue syndrome, fibromyalgia, and atypical depression.
Hypoactive HPA Axis
Chemicals in the brain, such as serotonin and norepinephrine, that transmit signals between nerve cells.
Monoamine Neurotransmitters
The extent to which genetic factors contribute to a trait or disorder.
Heritability
What is the connection between depression and HPA Axis?
One of the most consistent findings in psychiatry is the upregulation (increased activity) of the HPA axis in major depression. This is believed to play a role in the development (aetiology) and progression (pathogenesis) of the disease.
Most patients with severe depression show increased cortisol levels in saliva, blood, urine, and cerebrospinal fluid (CSF). They also exhibit an exaggerated cortisol response to ACTH and enlargement of both the pituitary and adrenal glands
The progressive loss of structure or function of neurons, including their death.
Neurodegeneration
What is the connection between depression and heart diseases?
Chronic inflammation from depression can contribute to the development of heart disease
Depression and cardiovascular disease (CVD) influence each other. This means that having one increases the risk of developing the other
Bi-directional Association of depression and cardiovascular disease
Inflammation can decrease GR sensitivity, and reduced GR sensitivity can increase inflammation
Bi-directional effect of inflammation and GR sensitivity
Support for neuron growth
Neurotropic
This is an amino acid that serves as a precursor (building block) for serotonin
Tryptophan
Can be converted into different metabolites.
Some, like kynurenic acid, are neuroprotective, while others, like 3-hydroxykynurenine and quinolinic acid, can be neurotoxic and contribute to conditions like depression
Kynurenine
Is a metabolite of the amino acid tryptophan and plays a role in various physiological processes, including immune regulation and neurotransmission
Kynurenine
Is a substance produced during metabolism
Metabolite
The process your body uses to convert food into energy and build or repair tissues.
Metabolism
Includes interactions between the nervous, endocrine, and immune systems
Neural Endocrine Immune Mechanism
How can we target inflammation-induced depression?
Identifying inflammatory biomarkers
Prevention of the development of depression involves understanding and managing inflammation.
Developing new treatments that target inflammation could improve outcomes for patients with depression
A part of the brain that can’t always distinguish between real and perceived threats
Amygdala
This automatic response is triggered by the amygdala
Fight or Flight Response
