MCB 165 Final Exam Questions
1. Does our brain shrink as we age?: Yes
- Ventricles are much smaller than in older people
- Loss of tissue in the front part of the brain is also seen
2. Describe the parabiosis experiment: Purpose: to see if there are molecules in the blood that
contribute to aging
1. Physically connect blood vessels from a younger mouse to an older mouse for ~ 5 months
--> Controls = 2 young mice connected and 2 old mice connected
2. Measure neurogenesis
--> Do this by looking for a protein called Dcx; this is a sign of a new neuron
3. What was found in the parabiosis experiment?: - In the experimental young mouse: decrease
in neurogenesis compared to young controls
- In the experimental old mouse: increase in neurogenesis compared to the old controls;
also increased blood flow, muscle rejuvenation, etc
- DIFFERENTIATING FACTOR: found a growth factor called GDF11 --> reversed signs of aging
in muscle and brain
4. What exactly is neurodegeneration?: A progressive loss of neurons and neu- ronal function
5. What is the general cause of many neurodegenerative diseases?: Excessive protein aggregation
6. What is the possible general pathway for why protein aggregates cause neurodegenerative
disease?: Occurrence to cause misfolded protein --> exposes hydrophobic regions --> causes
proteins to connect to each other in a way they weren't before --> forms soluble oligomers -->
continues to form beta sheets that stack on each other ==> fibrils (aka the aggregates)
7. What are the 3 hypotheses as to why protein aggregation is toxic and contributes to
neurodegeneration?: 1. Gain-of-toxic-activity hypothesis: protein deposits leads to neuronal
apoptosis --> neurodegen
2. Inflammation hypothesis: Misfolded and aggregated proteins --> excessive brain inflamm -->
neuron loss --> neurodegen
3. Loss-of-function hypothesis: loss of normal protein --> lack of biological activity
--> cellular malfunction and neuron loss --> neurodegen
- IN REALITY: all 3 are prob happening
8. What part of the protein aggregation process is thought to be the most toxic to neurons?:
Oligomers
9. Describe the experiment that showed how oligomers were the most toxic: - Had control mice,
mice w/ oligomers of amyloid plaque, and mice w/ fibrils of amyloid plaque
- FOUND
, MCB 165 Final Exam Questions
--> Controls: all neurons survived
--> Oligomers: 3/4 neurons died
--> Fibrils: 1/2 neurons died
10.What are the oligomers doing that make them the most toxic?: - Causes ER (and general) stress
- Can clog up the proteasome that usually clears them
- Some oligomers can form a pore and let in toxic amounts of Ca2+ in the cell
- They can interact w/ properly folded proteins and cause them to misfold
11.How can antibodies maybe help treat neurodegen diseases?: Have the antibody bind and
inhibit the oligomers
- They did create an antibody called W20: antibody that can bind to the beta sheets of multiple
oligomers
- FOUND: W20 improved memory impairments in mouse AD models and motor impairments
in Parkinsons and Huntingtins mouse models
12.What are prions ?: infectious proteins that have the ability to transmit their misfolded
shape onto normal variants of the same protein
--> can lead to protein aggregates
13.What was the first disease linked to a prion? Describe it: The prion PrP was linked to Mad Cow
disease
- Transmissible to humans from eating infected meat
- If not cooked properly, you might consume unhealthy prions --> float to your brain
--> cause your healthy prions to misfold
14.What is the basic genetic cause of Huntingtins?: CAG (glutamine) repeats in the Huntingtin
(htt) gene
15.What does the symptomatic progression of Huntingtins look like?: - Earli- est: difficulty
maintaining grip and chorea (involuntary body movements)
- Continuing: fine motor skill impairment, speech slurs, abnormal eye movements
- Worst: difficulty concentrating and multitasking, memory loss, dementia
--> is eventually fatal (w/in 10-20 yrs)
16.Which region of the brain expressed neuron loss first in Huntingtin? What symptom is it
connected to: Striatum
- Loss of medium spiny GABAergic striatal neurons --> causes increased output to the motor
cortex (you lose the "brakes" in motor functions)
- When D2 neurons die, neurons in the GPe will be more active and neurons in the thalamus (VL)
will be more active ’ means the motor cortex will be more excited/active
- Striatal D2R neurons selectively die
- What causes the motor symptoms
17.Where does neuron loss spread to after the striatum ?: Cortex
- Cognitive symptoms
1. Does our brain shrink as we age?: Yes
- Ventricles are much smaller than in older people
- Loss of tissue in the front part of the brain is also seen
2. Describe the parabiosis experiment: Purpose: to see if there are molecules in the blood that
contribute to aging
1. Physically connect blood vessels from a younger mouse to an older mouse for ~ 5 months
--> Controls = 2 young mice connected and 2 old mice connected
2. Measure neurogenesis
--> Do this by looking for a protein called Dcx; this is a sign of a new neuron
3. What was found in the parabiosis experiment?: - In the experimental young mouse: decrease
in neurogenesis compared to young controls
- In the experimental old mouse: increase in neurogenesis compared to the old controls;
also increased blood flow, muscle rejuvenation, etc
- DIFFERENTIATING FACTOR: found a growth factor called GDF11 --> reversed signs of aging
in muscle and brain
4. What exactly is neurodegeneration?: A progressive loss of neurons and neu- ronal function
5. What is the general cause of many neurodegenerative diseases?: Excessive protein aggregation
6. What is the possible general pathway for why protein aggregates cause neurodegenerative
disease?: Occurrence to cause misfolded protein --> exposes hydrophobic regions --> causes
proteins to connect to each other in a way they weren't before --> forms soluble oligomers -->
continues to form beta sheets that stack on each other ==> fibrils (aka the aggregates)
7. What are the 3 hypotheses as to why protein aggregation is toxic and contributes to
neurodegeneration?: 1. Gain-of-toxic-activity hypothesis: protein deposits leads to neuronal
apoptosis --> neurodegen
2. Inflammation hypothesis: Misfolded and aggregated proteins --> excessive brain inflamm -->
neuron loss --> neurodegen
3. Loss-of-function hypothesis: loss of normal protein --> lack of biological activity
--> cellular malfunction and neuron loss --> neurodegen
- IN REALITY: all 3 are prob happening
8. What part of the protein aggregation process is thought to be the most toxic to neurons?:
Oligomers
9. Describe the experiment that showed how oligomers were the most toxic: - Had control mice,
mice w/ oligomers of amyloid plaque, and mice w/ fibrils of amyloid plaque
- FOUND
, MCB 165 Final Exam Questions
--> Controls: all neurons survived
--> Oligomers: 3/4 neurons died
--> Fibrils: 1/2 neurons died
10.What are the oligomers doing that make them the most toxic?: - Causes ER (and general) stress
- Can clog up the proteasome that usually clears them
- Some oligomers can form a pore and let in toxic amounts of Ca2+ in the cell
- They can interact w/ properly folded proteins and cause them to misfold
11.How can antibodies maybe help treat neurodegen diseases?: Have the antibody bind and
inhibit the oligomers
- They did create an antibody called W20: antibody that can bind to the beta sheets of multiple
oligomers
- FOUND: W20 improved memory impairments in mouse AD models and motor impairments
in Parkinsons and Huntingtins mouse models
12.What are prions ?: infectious proteins that have the ability to transmit their misfolded
shape onto normal variants of the same protein
--> can lead to protein aggregates
13.What was the first disease linked to a prion? Describe it: The prion PrP was linked to Mad Cow
disease
- Transmissible to humans from eating infected meat
- If not cooked properly, you might consume unhealthy prions --> float to your brain
--> cause your healthy prions to misfold
14.What is the basic genetic cause of Huntingtins?: CAG (glutamine) repeats in the Huntingtin
(htt) gene
15.What does the symptomatic progression of Huntingtins look like?: - Earli- est: difficulty
maintaining grip and chorea (involuntary body movements)
- Continuing: fine motor skill impairment, speech slurs, abnormal eye movements
- Worst: difficulty concentrating and multitasking, memory loss, dementia
--> is eventually fatal (w/in 10-20 yrs)
16.Which region of the brain expressed neuron loss first in Huntingtin? What symptom is it
connected to: Striatum
- Loss of medium spiny GABAergic striatal neurons --> causes increased output to the motor
cortex (you lose the "brakes" in motor functions)
- When D2 neurons die, neurons in the GPe will be more active and neurons in the thalamus (VL)
will be more active ’ means the motor cortex will be more excited/active
- Striatal D2R neurons selectively die
- What causes the motor symptoms
17.Where does neuron loss spread to after the striatum ?: Cortex
- Cognitive symptoms
