Cell Death in CNS Flashcards
(39 cards)
What are the many different causes of cell death (7)?
- development (normal)
- trauma
- toxins (e.g. alcohol, pesticides, heavy metals)
- cerebral vascular disease
- infectious agents
- genetic diseases
- neurodegenerative diseases of unknown cause
What is multi-infarct dementia?
occurs when people have small mini strokes over time
- can cause or lead to dementia
- its temporary/transient strokes but has major overall consequences
what is Pick’s disease
its a cause of frontotemporal degeneration
- affects frontal and anterior temporal lobe areas
- posterior parts of the brain are undamaged
- causes atrophy and gyro become thinner and sulci deepen … cerebral ventricles become huge because surrounding tissue died off
What is huntington’s disease and how does it look like?
genetic disease
- shrinking of caudate nucleus and basal ganglia because of cell death
- ventricles are not round around the edges because its been dying off
how does parking sons disease look like in the brain?
less neural tracts in the substantia nigra compared to normal people
What is advanced CJD? how does it look like in the brain?
its mad-cow disease and brain cells die and look like sponge (bc of holes) and the brain overall has shrunked
what is meningioma?
tumor in the meningial linings
- its banging by itself but it cause harm to the brain if it keeps growing because its heavy and has a lot of pressure on the brain. it causes something called mass effect which is dents in the brain
it also compresses blood vessels and decreases blood flow to area
What is a brain that has alzheimers look like?
its shrunken
what does a brain of a person with alcoholism look like?
its very shrunken even more than alzheimers
how does the fetal alcohol brain look like?
its shrunken and slow development
What happens at a cellular level in neurons and glia?
- neurons are much more vulnerable than glia
- brain consumes 25% total oxygen and glucose in the blood stream
- neurons use glucose as their primary carbon source
- neurons are not replaced in significant numbers (but glia are)
What are some forms of appropriate cell death?
developmental die off –> appropriate
- during development, more neurons than will be needed are born
- fine tuning of connections orchestrated by interactions with the environment
- developmental cell death occurs without tissue inflame or disruption of surrounding cells
- use it or lose it principle that involves growth factors and electrophysiological activity
- this type of cell death is programmed by the DNA for establishment of the CNS and its appropriate
What is inappropriate cell death?
injury to the brain is any stimulus that brings changes in cell physiology and/or anatomy - internal or external
- injury can be reversible or irreversible
- adaptation results from the changes in cell due to reversible injury ONLY
- irreversible injury results in cell death
- whenever something takes neurons out of homeostasis state, it can result in cell death if the cell can fully adapt to the stimulus its reversible injury but if not, it will become irreversible and cause cell death (like stroke or head trauma)
What is glutamate-induced neuronal death?
also called excitotoxicity
- an event has caused cellular energy failure: disturbance causing lack of oxygen or glucose to cell (i.e. trauma or stroke)
this is excessive stimulation through receptors for neurotransmitter glutamate
- caused by excessive release, and failure of glutamate uptake mechanisms
- too much glutamate activity causes an imbalance of other ions such as calcium and sodium which results in cell death
- this will cause both DNA programmed and necrotic cell death
- glial cells clean up glutamate but they need ATP without o2 theres no ATP for glia theres no ATP for glia
What is reactive oxygen species cell death?
cell death caused by free radicals of oxygen
- will damage cell membranes and intracellular organelles
- will activate DNA programmed cell death mechanisms
What is hypoglycaemia causing cell death?
low glucose levels
- loss of glucose leads to rapid depletion of cellular energy reserves
- will activate DNA programmed cell death mechanisms
What are some ways that free radicals are formed? (6)
- ionizing radiation
- smoking
- air pollution
- inflammation
- metabolism
- UV light
What are two main modes of inappropriate cell death?
- necrosis –> rapid, somewhat messy death via induced inflammation
- apoptosis –> programmed cellular suicide … has a window of opportunity of recovery unlike necrosis and its slower
What is Necrosis?
dramatic and very rapid form of cell death in which every compartment of the cell disintegrates… outer cell membrane ruptures and releases its intracellular contents
what is necrosis characterized by?
dysregulation of ion homeostasis (dissociation between inner and outer membrane) causing:
- cell swelling
- dilation of mitochondria and ER
- formation of vacuoles in cytoplasm
- activation of enzymes called proteases, which degrade cellular components (normally these proteases are held in lysosome packages but necrotic process release them) proteases cause neighbouring cells to rupture and inflammatory agents to start moving into those regions
What happens during cell death in necrosis?
- chromatin clumps and nuclear membranes are disrupted
- gene transcription and protein synthesis stops
- ATP is rapidly depleted
- cells lyse and spill their contents into the ECF
- contents can damage neighbouring cells
- spillage causes inflam response
What kind of cells go through necrosis and apoptosis.. what does it depend on?
there are very few cell deaths that trigger only capable of inducing either necrosis or apoptosis, they usually occur together
whether a cell undergoes apoptosis or necrosis is determined primarily by the intensity and/or duration of the death-inducing stimulus
- if a stimulus is severe and/or sustained it will induce necrosis (i.e. glutamate/excitotoxicity)
- if stimulus is less severe with transient stresses (comes and goes) it will induce apoptosis (i.e. energy failure/ischemia)
What is the process of Apoptosis (aka Type 1 PCD)?
there are multiple forms of programmed cell death (PCD) but apoptosis is the best characterized form of it
- apoptosis occurs in both appropriate and inappropriate cell death (i.e. like during development)
What are two main pathways of apoptosis?
- intrinsic –> generated by signals arising within the cell
- Extrinsic –> triggered by death activators binding to receptors at the cell surface
both pathways join together to make a final common pathway
there is also a direct-to-DNA pathway called Caspase-Independent pathway (doesn’t require intrinsic or extrinsic enzymes)
