LG 2.13 Neuronal Cell Death Flashcards
Describe the metabolic consequences of hypoxia/ischemia and the features of necrotic cell death?
Hypoxia-ischemia eliminated ATP production, leading to ionic imbalances that have vast metabolic consequences
Describe the morphological and molecular features of apoptosis?
Apoptosis causes laddering of DNA, karyolysis, and blebbing of cytoplasm.
Outline the contribution of apoptosis to ischemic brain injury?
Apoptosis can be triggered by cellular signals in injured cells, particularly by mitochondrial damage
Differentiate between necrosis and apoptosis/programmed cell death?
Oncosis leads to inflammation, apoptosis does not, but both can be triggered by hypoxia-ischemia
State the role of cell death in neural development and neurodegeneration?
Development of the neural system requires cellular rearrangement and pruning to create the complex cellular systems and morphology in the brain
How does apoptosis affect embryonic development?
- During embryonic development, the nervous system is “Sculpted” by neuronal cell death
- Excess neurons are removed to ensure proper and precise synaptic connections
Would regulation of apoptosis be considered the role of a proto-oncogene or a tumor suppressor gene?
Tumor suppressor gene
When does ischemia occur?
Ischemia of the brain usually occurs when blood flow drops below 25% of normal perfusion levels
What is another word for the core?
Umbra
What is the penumbra?
Outside the umbra
Treatment of a thrombo-emboli with a form of plasmin will save the neurons from damage as perfusion has been restored.
No. Most damage comes from reperfusion injury
What is excitotoxicity?
– nerve cells are killed by excessive neurotransmitters
What is oxidative stress?
reactive oxygen and nitrogen species destroy cellular structures
What is apoptosis?
programmed cell death
How do NMDA affect excitotociciy?
- NMDA receptors create fast excitotoxicity (>3 min) by increasing [Ca2+]i and interfering with calcium proteins in the cytoplasm
- Activation of calpains and cathepsins
- Activation of phospholipase A and C
- Activation of Calcium dependent protein kinases
What will the activation of Phospholipase C probably not directly do to the cell?
Destroy the DNA through enzymatic degradation
“Electrophoretic uniporter powered by the negative membrane potential?” Seriously? What the frick is that?
Natural electrical “drag” of cations into the cell because of free electrons in the matrix
How does Mitochondria and Ca2+ affect each other?
- Intake of excessive Ca2+ impairs oxidative phosphylation
- Lack of ATP prevents ATP-dependent Ca2+ pumps
- Mitochondrial permeability increase releases cytochrome C, etc., into cytoplasm
What is the main differences between Oncosis and Necrosis?
- No nuclear disruption is evident (opposite of apoptosis)
- No inflammation
Oncosis can probably be influenced by tumor suppressor genes.
No, because tumor suppressor genes probably cause apoptosis, and oncosis is induced by cellular damage.
What do you think will happen when reperfusion of the tissue is achieved?
- Hypoxic-ischemic damage has caused [Ca2+]i increase
- Hypoxic-ischemic damage has shut down the mitochondria
- Oxygen will have nowhere to go inside of the cell
Which molecule serves as an anti-oxidant to ameliorate oxidative damage to cells?
Glutathione
What generates ROS?
Lack of ATP, uncoupled electron transport, and re-perfusing oxygen generate ROS
What also causes ROS?
Ferrous ions also increase ROS
Note: cyclooxygenase activity increases after reperfusion
What type of NO protects against hypoxia?
eNO
What can diffuse to adjacent damaged neurons and convert to a free radical and damage DNA?
nNO
What does endothelial NO do in the brain?
It causes an increase in perfusion to the tissues
What will create inflammatory chemicals in Oncosis?
Cyclooxygenase will create inflammatory chemicals
What does p53 activate?
Apoptosis
What are two methods of activating apoptosis?
-Caspase cascade and cytochrome C
What does caspases require for activation?
Calcium
Does apoptosis cause inflammation?
No inflammation involved
Why is inflammatory cytokine production probably not the best thing near neurons?
Movement of white blood cells in the tissues probably would disrupt synapses
What is ROS?
Reactive oxygen species
