Lectures 3 & 4

Question 1

What are splice variants? How are knock-in mice different from knock-out mice?

Answer 1

A genetic alteration in the DNA sequence (happens at boundry of exon and intron).
In knock-in mice a native gene is replaced with a modified one. Knockout mice have had a gene deleted or “knocked out”.

Question 2

What is the main source of ATP in neurons?

Answer 2

mitochondrial oxidative phosphorylation.. meaning that most of a neuron’s ATP is generated within the mitochondria through the process of oxidative phosphorylation, using glucose as the primary energy source

Question 3

How does HRP or herpes virus get to neuronal somas?

Answer 3

They exploit retrograde transport to infect neurons. For example, the oral type of herpes enters axon terminals in the lips and mouth and is transported back to the parent cell bodies. Once in the soma, it replicates, killing the neuronal host, and then is taken up by other neurons and repeats the process until the victim dies.

Question 4

What is a Fragile X syndrome? How does it affect dendritic spines?

Answer 4

A disorder that manifests as intellectual disability and autism and is caused by disruption of a single gene.
Unusual changes in dendritic spines have shown to occur in the brains of individuals with cognitive impairments. Such unusual changes would resemble thin gangly strands hanging off of the spine.

Question 5

Describe 3 features of pyramidal cells. What are interneurons?

Answer 5

1. They are pyramid shaped.
2. In the cerebral cortex pyramidal cells have long axons that extend to other parts of the brain and are therefore Golgi type I neurons.
3. In the cerebral cortex all pyramidal cells are spiny. The spines are basal (at the base) dendrites that extend horizontally.

Neurons that only form connections in the nervous system to other neurons.

Question 6

What are the methods used to precisely distinguish between subtypes of neurons? What distinguishes one neuronal subtype from another if both of them have identical morphological appearance?

Answer 6

Methods to distinguish subtypes:
Connections - what kind of message is delivered in the body (ex: sensory or motor neurons)
Axon Length
Gene Expression - What neurotransmitter do they use?
Number of Neurites (axons and dendrites) that extend from the soma (ex: unipolar, bipolar, multipolar)
Dendrites - stellate (star shapes) or pyramidal.

Question 7

Name 5 subtypes of glial cells. Which are the smallest and most mobile glial cells?

Answer 7

Astrocytes - most numerous and maintain homeostasis.
Oligodendrocytes - form membranes to insulate axons in central nervous system
Microglia - immune cells of the brain. SMALLEST AND MOST MOBILE.
Schwann cells - form membranes to insulate axons in peripheral nervous system
Satellite cells - surround neuronal cell bodies in peripheral ganglia as protection

Question 8

What is the difference in myelination in CNS vs PNS? Consequences of demyelination in the CNS vs PNS?

Answer 8

1. Myelinating cells - In the CNS, oligodendrocytes form myelin, while in the PNS, Schwann cells form myelin.
2. Number of axons myelinated - In the CNS, one oligodendrocyte can myelinate multiple axons, while in the PNS, one Schwann cell forms a single myelin sheath.
3. Myelin structure - In the CNS, the number of myelin layers can vary along the length of the myelinated segment, while in the PNS, the number of layers is relatively uniform.
4. Myelin protein composition - PNS myelin contains a positively charged protein called P2, while CNS myelin lacks a dense line structure.
5. Axon diameter - In the PNS, myelinated axons are more than 1–2 μm in diameter, while in the CNS, almost all axons with diameters greater than 0.2 μm are myelinated

The primary difference in consequences of myelination between the central nervous system (CNS) and peripheral nervous system (PNS) is that damage to CNS myelin, produced by oligodendrocytes, often leads to significantly reduced regeneration potential and more severe functional impairments compared to PNS damage where Schwann cells can facilitate axon regrowth, due to the distinct cellular mechanisms involved in myelination in each system; essentially, CNS damage is less likely to recover fully compared to PNS damage.

Question 9

Describe and distinguish between Multiple Sclerosis and CMT diseases

Answer 9

MS - an autoimmune neurological disorder where victims complains of weakness, lack of coordination, and impaired speech and vision. MS attacks the myelin sheath of bundles of axons in the brain, spinal cord, and optic nerves (immune system attacks the CNS)

CMT Diseases (Charcot-Marie-Tooth) also affects the nervous system. CMT is a hereditary polyneuropathy that affects the PNS as opposed to the CNS like MS does.

Question 10

Why is blood brain barrier important and what glial cells contribute to its function the most?

Answer 10

The BBB helps limit the movement of potassium (and other bloodborne substances) into the extracellular fluid of the brain. The Astrocytes aide in this endeavor. They have membrane potassium pumps that concentrate the potassium in their cytosol. They also have potassium channels that regulate potassium through potassium spatial buffering.

Question 11

What is a fluid mosaic model of plasma membrane?

Answer 11

A membrane is a mosaic of components - phospholipids, cholesterol, proteins, and carbs.

Question 12

Name three cytoskeletal elements from the smallest to the largest. How is their cellular location different?

Answer 12

1. Microtubules (20nm)
2. Neurofilaments (10nm)
3. Microfilaments (5nm)

MT are located longitudinally down neurites. MF are found throughout neurons but are primarily in neurites
NF are found in all neuron cells.

Question 13

What are two major cellular pathological hallmarks of Alzheimer’s Disease? What is a comorbidity?

Answer 13

1. Amyloid Plaques - Beta Amyloid (extra cellular)
2. Neurofibrillary Tangles - protein on microtubules, and accumulation in soma.