LECTURE Excitotoxicity Flashcards
Which of the following is produced almost exclusively in the midline raphe nuclei?
A. Dopamine B. Epinephrine C. Norepinephrine D. Histamine E. Serotonin
E. Serotonin
A patient develops an auto-immune disorder that causes the destruction of neurons that release histamine as their neurotransmitter. What part of the brain was damaged in this disorder?
A. The Locus Coeruleus
B. The Raphe nuclei
C. The Substantia Nigra pars compacta
D. The Tuberomammillary nucleus
D. The Tuberomammillary nucleus
What is the correct order of neurotransmitter production in neurons who make neurotransmitters based on the amino acid tyrosine?
A. Dopamine – Epinephrine – Norepinephrine
B. Dopamine – Norepinephrine – Epinephrine
C. Epinephrine – Dopamine – Norepinephrine
D. Epinephrine – Norepinephrine – Dopamine
E. Norepinephrine – Dopamine – Epinephrine
F. Norepinephrine – Epinephrine – Dopamine
B. Dopamine – Norepinephrine – Epinephrine
***Use L-Dopa because it can get past BBB
Which of the following neurotransmitters is derived from tryptophan?
A. Dopamine B. Epinephrine C. Histamine D. Norepinephrine E. Serotonin
E. Serotonin
Dr. Karius is studying NMDA receptors, so she stimulates the neurons in culture with NMDA. Shockingly, she is unable to record an epsp after the stimulation. What does she need to add in order to elicit an epsp?
A. Glycine B. Glutamate C. Mg++ D. PCP E. Valium (a benzodiazepine)
A. Glycine – because it is a co-agonist required for NMDA receptors
B. Glutamate – because it is an EAA which is required to depolarize the Non-NMDA receptor to get the Mg++ out of the NMDA receptor.
Which of the following neurotransmitters is believed to have a large number of extra-synaptic receptors in the brain?
A. Acetylcholine B. Dopamine C. GABA D. Glutamate E. Histamine
C. GABA
***On locations outside of synapse - important for general anesthetics because they hyperpolarize all neurons and make you go to sleep
Activation of which opiate receptor is associated with analgesia alone?
A. Mu receptors
B. Delta receptors
C. Kappa receptors
B. Delta receptors
Dr. Karius is developing a research program to investigate the role of the CB1 receptor in neuroprotection, but she wishes to avoid the legal implications of using the “traditional” agonist for these receptors. What endogenous substance could she use to produce the same effects?
A. AMPA B. Anandamide C. Aspartate D. CBD (cannabidiol) E. Dynorphin F. Nociceptin
B. Anandamide
Student Dr. Seuss, like most medical students, is chronically sleep deprived. Sadly, that means that he fell asleep while listening to Dr. Karius drone on about neurotransmitters. Which of the following neurotransmitter/receptor pairs was activated to make him fall asleep?
A. Adenosine/P1 B. ATP/P2X C. Glutamate/AMPA D. Histamine/H1 E. Leu-enkephlin/Mu-opiate receptor
A. Adenosine/P1
Activation of which of the following receptors is directly associated with the influx of Calcium into the post-synaptic neuron?
A. Glycine B. Nicotinic Cholinergic C. Muscarinic Cholinergic D. NMDA E. AMPA F. GABA-A G. GABA-B
D. NMDA
What are the three things that are vital to our normal brain function?
- EAA neurotransmitter system
- Calcium
- Oxygen
T/F. Over-stimulation of the EAA system occurs after ischemia in the brain and is responsible for damage to neurons whether or not they were exposed to the ischemia.
True
Substantial evidence for involvement of over-stimulation of the EAA system occurs in which situations?
Strokes Global hypoxia or anoxia Traumatic injury to brain Hypoglycemia Epilepsy
***Anything that impairs our ability to maintain ATP in neurons!
For example, in a stroke, it starts with a localized event and an immediate loss of blood flow. Within 4 minutes, ________ levels drop to zero near the mitochondria and ATP production ceases. This drop in ATP causes the _________ activity to drop quickly as well. This in turn causes the depolarization of the neuronal cell membrane.
Oxygen
Na/K ATPase
In a stroke, remember the resting Vm was the equivalent of pushing the ball up the hill (requires ATP). The action potential was the equivalent of the ball rolling down the hill. As the neurons depolarize, they reach threshold and the voltage-gated ________ channels open leading to action potentials.
Sodium
In a stroke, once the action potentials reach the presynaptic terminal, the inevitable happens. There is release of the NT into the synaptic trough/cleft and because there are so many synapses in the cortex using _______, this results in a lot of ______ being released into many different parts of the brain.
EAA
EAA
***The whole brain is affected, not just the area of ischemia!
In a stroke, the problem is that without ATP the EAA can’t be taken up by the ________ cells like usual. The uptake of the EAA is dependent on secondary active transport of Na+, which requires ATP. So the uptake process is shut down and EAA continues to accumulate in the synapse.
Glial
Many synapses express both non-NMDA and NMDA receptors, and the activation of non-NMDA produces the depolarization that will force the ________ out of the ________ channel. In a stroke, because of the large amount of constant depolarization, there is a LOT of ________ in the postsynaptic cells.
Mg++
Calcium
Calcium
What are the 4 consequences of having high intracellular calcium (in postsynaptic cell specifically)?
1) Increase in Phospholipase A
2) Activation of u-calpain (a proteolytic enzyme)
3) Activation of calcineurin
4) Activation of the apoptotic pathway
Increased intracellular calcium can in the activity of Phospholipase A. This acts on the membrane to release _________ _________, which can cause physical damage to the membrane when it is activated a lot.
Arachidonic Acid
Arachidonic Acid can become another messenger and lead to:
– ________ release from the ER and mitochondria
– Unfolded protein response by causing the ______ to stop making proteins
– eIF2a-kinase activation
– Mitochondrial dysfunction
Calcium
ER
High concentrations of intracellular calcium can activate u-calpain (a proteolytic enzyme) which can cause the proteolysis of structural proteins such as ________. It can also cause the proteolysis of other enzymes and proteins including eIF4G. The leads to the _________ and _________ impairment of neurons.
Spectrin
Metabolic
Structural
High concentrations of intracellular calcium can activate calcineurin, which causes excess production of _______ _______ by activating the enzyme _______ _______ _______.
Nitric Oxide (NO) Nitric Oxide Synthase (NOS)
Excess Nitric Oxide is bad because it can produce…
Free radicals
High concentrations of intracellular calcium can also activate the apoptotic pathway. Specifically, it releases calcium from intracellular stores which causes the mitochondria to release enzymes, including _________. This leads to the activation of _________, which is pro-apoptotic and will result in the death of the neurons.
Caspase 9
Caspase 3
At some point, oxygen has to try to make a comeback (reperfusion), but because of the changes that have occurred in the cell that will not be easy. Remember, mitochondria have released many of their enzymes already, which impairs their ability to use oxygen to make ATP. What’s going to happen to the oxygen now?
Free radicals
Some mitochondria can still be able to synthesize ATP, but a different set of proteins are now active compared to in the healthy state. Kinases will take the ATP and turn it into ADP and PO4. Phosphorylation is a further modifying enzyme action. Specifically, the phosphorylation of _______ kinase leads to a further decrease in protein synthesis and further activates _________, which further increases apoptotic signaling!
eIF2a
Caspase 3
