2.13 MCB - Neuronal Cell Death Flashcards
During embryonic development what occurs in order to sculpt the nervous sytem and ensure proper and precise synaptic connections?
Neuronal cel death.
Excess neurons are removed.
Give an overview of what occurs in apoptosis? (type of signals sent out, what becomes activated, what does this further activate, what becomes destroyed and leads to cell death).
Paracrine or autocrine signals.
Activate death domain receptors. Further activate caspase family.
Cell nucleus is destroyed, and leads to cell death.
How are apoptotic cells broken down in order to be easily removed from their location?
Blebbing of the cells and nuclear destruction create small cellular packages.
These cells are then easily removed by phagocytosis.
Would regulation of apoptosis be considered the role of a proto-oncogene or a tumor suppressor gene?
Tumor suppressor gene.
Proto-oncogenes are usually involved with something that results in cell growth.
When ischemia or hypoxia occurs what happens to the grouping of cells that are not receiving blood (what are they called?), and what happens to the area of cells surrounding the original grouping (what are they called?)?
Umbra - cells not receiving blood.
Penumbra - cells next to umbra cells.
Umbra cells die rapidly followed later by the surrounding penumbra cells.
What is the 2-phase pattern of cell death regarding hypoxia/ischemia? (don’t think too hard).
Basically what occurs in the last card.
Immediate death of core neurons directly affected by hypoxia-ischemia. and Later death of neurons that had no hypoxic-ischemic insult.
What is repurfusion, regarding hypoxia-ischemia?
Repurfusion is cell damage after circulation is restored. Secondary damage post initial traumatic event.
Name and describe the three distinct pathways that create problems during hypoxic-ischemic insults.
Which are specific, which are non-specific?
Excitotoxicity: nerve cells are killed by excessive neurotransmitters (glutamate). SPECIFIC.
Oxidative Stress: reactive oxygen and nitrogen species destory cellular structures. NON-SPECIFIC.
Apoptosis: programmed cell death. SPECIFIC.
Describe the mechanism of excitotoxicity beginning with decreased ATP production.
Decreased ATP production => increase in [Ca+] in axon terminals (don’t forget that Ca+ is actively removed from axons in order to keep the concentration low).
Increased [Ca+] => increased vesicle fusion.
Increased vesicle fusion => excess amounts of glutamate (or NT) in synapse.
Lack of ATP => astrocytes stop uptake of glutamate.
What role does glutamate have on the postsynaptic cell? What would be the ultimate end of this process? (think back on Pong’s lecture).
Increased [Ca+] in postsynaptic neuron.
Activation of calpains and cathepsins, activation of phospholipase A and C, activation of calcium dependent protein kinases.
During excitotoxicity, what would happen to the [Na+] concentration in the postsynaptic cell? What would this lead to?
[Na+] increase.
This would increase cytoplasmic volume and cause oncosis or necrosis.
Mitochondrial swelling, cytoplasm vacuolization, swelling of the nucleus and cytoplasm.
Eventual death of the cell.
The influx of Ca+ during excitotoxicity can also activate certain enzymes. What are these enzymes, what do they do?
Activate Ca2+/Mg2+-dependent endonucleases.
These endonucleases chew up the DNA into small bits (show up on a gel as small fragments) => destroy DNA.
Our brains use a ton of the bodies ATP, mitochondria as a result are very prevalent in neuronal cell bodies. These mitochondria have a negative charge and can take in Ca+ by electrophoretic uniporter. What is that? What happens to the Ca+ present in the mitochondria in a healthy system? What happens in the mitochondria when there is an excess of Ca+ in the system?
Electrophoretic uniporter: powered by negative membrain potential causes natural pull and sucks in Ca+.
Healthy system: Ca+ is removed from mitochondria using ATP.
Excess Ca+: impaires oxidative phosphorylation => lack of ATP being produced prevents Ca+ pumps => lack of ATP in cell => mitochondria physically break down (excess O2 in mitochondria as well).
What is oncosis? How does it differ from apoptosis (regarding visualization of cells)?
Oncosis: necrosis of neurons.
Na+ and Ca+ increases into the cell results in massive influxes of H20 and Cl-. This results in cellular swelling and organelle swelling.
No nuclear disruption is evident. In apoptosis there is nuclear disruption.
Oncosis can probably be influenzed by tumor suppressor genes?
No, because tumor suppressor genes probably cause apoptosis, and oncosis is induced by cellular damage.
