exam 3 study guide Flashcards
What are the diverse cell types involved in responses to CNS insults
CNS intrinsic neuronal cells
CNS intrinsic non neuronal cells
CNS extrinsic cells that enter from the circulation
a nonspecific reactive change of glial cells in response to CNS insults, involving the proliferation or hypertrophy of all 3 types of glial cells, including astrocytes, microglia, and oligodendrocytes
reactive gliosis
The major function of macrophages in multicellular responses to CNS insults?
Phagocytose + remove debris
necrosis P apoptosis, clot formation, inflammation
phase 1
Cell proliferation for tissue replacement. Fibrotic scar formation, reactive gliosis and astrocyte scar formation
Phase 2
Tissue repair & remodeling. BBB repair, remodeling of fibrotic and astrocyte scar, synapse & circuit remodeling, and remyelination
Phase 3
What are the major components of the glial scar?
astrocytes, microglia/macrophages, CSPGs
Seals the lesion site
CSPGs can inhibit axonal growth
Regulate immune response (temporal and spatial control)
Control neurogenesis
major features and functions of the astrocyte scar
The scar tissue is required in the acute phase after injury for sealing and cleaning the injury and restoring homeostasis but needs to be degraded at later (chronic) phases for axon regrowth
The timing of scar generation/degradation are crucial in determining its effects
Can chronic diffuse insults trigger reactive gliosis and multicellular responses?
Yes
What is the consequence of multicellular responses to diffuse insults in neurodegenerative diseases?
These regions can affect synaptic interactions and neural circuit functions
any endogenous substance that signals tissue and cell damage
Alarmins
Danger‐Associated Molecular Patterns. Host molecules that can initiate a noninfectious inflammatory response
DAMPs
recognize altered self-molecules such as DAMP and can activate to clear altered self debris
Pattern Recognition Receptors
exogenous molecules associated with groups of pathogens that initiate the inbfectious pathogen inflammatory response
PAMPs
What are the sources of the molecular signals that regulate reactive gliosis?
ALL THE ABOVE IS THE ANSWERRRRRRRRRRRRRR
Where does IL-1β come from
microglia
stimulates 1) local reactive astrocytes to release VEGF and 2) local OPCs to release MMP‐9 which in turn influence tight junctions and barrier properties of local endothelial cells and allow entry of serum proteins
IL-1β functions
What is the major source of the molecular signal that regulates neural remodeling in perilesion perimeters?
reactive gliosis
what are the two major categories of extrinsic inhibitors from the glial environment in the CNS injury site?
Myelin- associated inhibitors
CSPGs
What are myelin-associated inhibitors
-regulate axon growth
Nogo
(MAG)
(OMgp)
(Sema4D/CD100) and (ii) ephrin B3
the inhibitory effect of CSPGs can be eliminated by which enzyme?
ChABC
Receptors: NGR, p75, Troy, Lingo1
Effectors: RhoA, ROCK, LIMK, Cofilin, Actin
receptors and the intracellular signaling pathways for myelin-based inhibitors
How do risk factors of stroke increase its propensity
Risk factors have major effect on the structure and function of blood vessels
how do they alter cerebral blood vessels
risk factors increase ROS (reactive oxidative species) which causes inflammation in cerebral blood vessels
**Which of the following statement about stroke is not correct
risk factor has profound effect on nervous system
a meta‐stable zone characterized by significantly depressed tissue perfusion that is barely sufficient to support basal ATP levels, oxygen metabolism, and normal ionic gradients, salvageable
Ischemic penumbra
irreversibly damaged tissue distal to an occluded blood vessel, characterized by <20% of baseline blood flow levels, depleted ATP stores, and irreversible failure of energy metabolism and is nonsalvageable
ischemic core
integrates responses in all cell types, including vascular, glial, and neuronal elements and the matrix components
neurovascular unit
What is the major damage that causes functional deficits in spinal cord injury?
Interruption of long ascending and descending spinal tracts
What is the neuronal plasticity after spinal cord injury
Adaptive reorganization of neural pathways after injury + major cause is Collateral sprouting
T/F: spontaneous neuron plasticity is mostly due to regrowth or regeneration of neuron axon
FALSE its due to collateral sprouting
What are mechanism we should consider when we develop something for spinal cord injury
ALL THE ABOVE
What is sensorineural hearing loss (SNHL), which cells and tissues are damaged in SNHL?
damage to the sensory hair cells (inner hair cells and outer hair cells) in the cochlea, or to the spiral ganglion neurons (SGNs) or the eighth cranial nerve
T/F spontaneous neuronal plasticity due to regeneration
f
- Genetic or hereditary
- Overexposure to sound (noise)
- ototoxic drugs
- infection or immune-induced inflammation
- aging
common causes of sensorineural hearing loss?
stress-activated protein kinase/JNK, and p38
stress signaling pathways
ERK1/2 pathway, PI3K/PKC/AKT signaling pathway, Anti-apoptotic signaling pathway, Purinergic Pathways
survival signaling pathways
age related hearing loss
presbycusis
hair cells can be regenerated from supporting cells through which two mechanisms?
Mitotic regeneration
Direct transdifferentiation
What are the potential strategies to manipulate the hair cell developmental cues to promote hair cell regeneration? **MC/MA
Down: p27, notch, shh
Up: Atoh1, Wnt, FGL
- Generate neurons or oligodendrocytes, never both
- Subventricular zone
- Generates neurons and astrocytes, not oligodendrocytes
- Sub granular zone
- Self-renewal
- Quiescence
- Differentiation capacity
- Heterogeneity
- Residence within a specific environment (AKA stem-cell niche)
- Only have multipotency not pluripotency
What are the fundamental properties of adult neural stem cells (NSCs)?
cell types (cellular architectures) in adult NSC niches
- Ependymal + vascular cells, astrocytes, transient amplifying progenitor cells, and neuroblasts
- ECM
- Morphogens
- growth factors
- neurotrophins
- Neurotransmitters
- direct cell-cell interaction molecules
- Circulating factors (cytokines)
types of signaling molecules in adult NSC niches that can influence adult NSC behaviors
- additional layer of plasticity to the brain
- important for certain types of learning and memory
- produce a small but significant proportion of glia
- produce autocrine and paracrine signaling
potential functions of adult NSC
Where are ES cells derived from and what are the properties of ES cells?
Derived from: inner cell mass of mammalian blastocysts
Self-renewal
Pluripotency
ability of stem cells to differentiate into any cell types of 3 germ layers that make up the body
Pluripotency
stem cells. Can form any cell types, including all the cell types in a body, plus the extraembryonic or placental cells
Totipotency
cells can develop into more than one cell type but not any cell types
Multipotency
the hallmarks of pluripotency of a stem cell line
chimeric animals + teratoma formation
ES cells derived form ICM hold naïve or ground state _____ an have developmental capacity to generate all cell types of 3 germ layers in our body, including germline
pluripotency
Epiblast stem cells derived from the post-implantation epiblast adopt a ‘___’ pluripotent state and show a more restricted potency
primed
- scnt
2.fusion with a pluripotent stem cell
(3) transduction of reprogramming factors
(4) exposure to small chemical compounds.
What methods can be used to reprogram differentiated cells
Sir John Gurdon used_____ to reprogram differentiated somatic cells to become pluripotent
scnt
Dr. Shinya Yamanaka used reprogramming factors to reprogram differentiated mature cells into ESC-like cells called ____
are induced pluripotent stem cells (iPSCs)
what are the four factors that Dr. Shinya Yamanaka introduces into somatic cells to generate iPSCs?
OCT3/4, SOX2, KLF4, c-MYC (OSKM)
WHICH OF THE FOLLOWING IS NOT CORRECT ABOUT STEM CELLS
HAS PLURIOPOTENCY (that is false cause it is multipotent)
direct conversion of one differentiated cell type into another without transition through a pluripotent cell state
Direct lineage programming/ transdifferentiation
How to achieve direct lineage reprogramming?
LINEAGE SPECIFIC TRANSCRIPTION FACTOR
if you would like to direclty reprogram mouse fibroblasts into induced motor neurons, would would you do
introduce BAM factors and motor neuron lineage specific transcription factors into fibroblasts
Which cells are the most ideal starting candidate cell type to generate new neurons from non-neuronal cells?
astrocytes
What is neuronal plasticity during neuronal reprogramming? Can we generate neurons from other subtypes of neurons of all ages?
Mechanisms in place to postmitoticallly to progressively restrict neuronal fate potential and reprogramming capabilities as neurons age
When we perform the pluripotent stem cell‐based replacement therapy for treating neurologic disease, which diseases are more amenable and which are not good targets? ***MC/MA
Poor: AD, LBD, MSA, ALS, SMA
Amenable: PD, HD, MS, lysosomal storage disorders
Astrocytes don’t have signals with surrounding tissue
f
*****T/F: SGZ NSCs generate neurons and astrocytes, but not oligodendrocytes
t
(T/F) astrocytes dont send signals to surrounding tissues
f
*****T/F; Original function of NSC is to regenerate
f
**Four factors that Dr. Yamanaka introduces
OCT3/4, SOX2, KLF4, c-MYC (OSMK)
humans have epiblast stem cells t/f
t
rodents have only ground state
f have naive nd ground
*****What are the mechanisms that we should consider when developing repair strategies for spinal cord injury?
ALL OF THE ABOVEEE
*****T/F: In the SPI, there is regeneration of the neurons action
f
***T/F Major functional deficit is due to neuronal cell death
f
**T/F Protect neuronal and then glial
FALLSEEEE YOU NEED TO PROTECT THEM ALL AT THE SAME TIMEEEE
T/F: Risk factors for strokes affects the structure and function of nervous system
f
***** (T/F) CSPG is a myelin-associated inhibitor.
f
**DAMPS,ALARMINS,PRPRS, NI-REGS, AND PAMPs
ALL OF THE ABOVE
How do risk factors of stroke alter the cerebral blood vessels
It increases ROS which causes inflammation in cerebral blood vessels
**damage to which of the following parts of the auditory system would not result in sensorineural hearing loss
auditory cortex
**Which of the following factors is not a major cause of acquired sensorineural hearing loss
genetic mutation or smoking
*****intracellular mechanism of HC loss
free radical calcium accumulation
MAPK signalling pathways and apoptosis
infection,immunity, and inflammation
*****What is the most common form of SNHL
ARHL or presbyscusis
**are CPGs reflexive or voluntary?
NEITHER
**Know the cells in the cochlea
inner hair cell
outer hair cell
supporting cell
**The functional deficit of SPINAL CORD INJURY is due to cell death (T/F)
A
FALSSEEEEE- the pathway got damage (ascending/descending spinal tracts)
*****During the stroke, which of the following cells do you need to protect first
Neuron, microglia, oligodendrocytes (can’t just protect one)
–
**What is the signal that stimulates reactive gliosis
All of the above- regulated by everything.
