N480 - CHAPTER 50 EXAM QUESTIONS WITH CORRECT ANSWERS LATEST UPDATE 2026
What occurs during Wallerian degeneration - Answers anterograde degeneration of the axon terminal
(distal to the site of injury).
What occurs during the chromatolytic reaction - Answers Nissl substance (the aggregation of ER and
associated ribosomes) spreads throughout the neurites becoming fragmented. The cell body swells
and the nucleus moves to an eccentric position.
Effects on downstream/postsynaptic neurons - Answers downstream neurons begin to die because
they are not innervated.
Effects on upstream/presynaptic neurons (synaptic stripping, etc.) - Answers presynaptic neurons
retract from the dying neuron and are replaced by processes of glial cells. This decreases synaptic
activity and can impair recovery.
Effects on glial cells (oligodendrocytes, Schwann cells, reactive astrocytes, microglia) - Answers
Schwann cell response in axotomy - Answers will break myelin into small fragments and engulf it, they
also secrete factors to recruit macrophages and stimulate axon regeneration.
Macrophage response to axotomy - Answers help Schwann cells to clear up fragmented myelin.
Oligodendrocyte function in axotomy - Answers cannot dispose of the fragmented myelin and instead
rely on microglia.
Reactive astrocytes - Answers form glial scars in response to axotomy.
Delineate the core pathway that regulates axon degeneration following axon injury in mice - Answers
The enzyme NMNAT2 promotes the conversion of NMN to NAD, which is key for generating ATP and
promoting axonal integrity. NMNAT2 also inhibits SARM1, which is an enzyme that degrades NAD into
NAM. NMNAT2 is transported down the axon from the soma in uninjured axons.
NMNAT2 pathway in damaged axons - Answers NMNAT2 cannot travel down the injured axon, and so
cannot promote the formation of NAD. It also fails to prevent NAD breakdown by SARM1. This leads
to rapid depletion of NAD and cessation of ATP synthesis which increases [Ca2+] and promotes axon
degeneration.
Wlds mutant mechanism - Answers this mutant possesses a mutated NMNAT1 protein, which
mislocalizes to the axon instead of remaining in the nucleus. NMNAT1 degrades more slowly than
NMNAT2, allowing it to sustain [NAD] in the axon, staving off axon degeneration. Effects last for 10-12
days after injury.
SARM1 knockout mechanism - Answers the absence of SARM1 allows [NAD] to persist for a time in
spite of axotomy, delaying axon degeneration.
Axon regeneration in the CNS and PNS - Answers
Explain why axons in the PNS regenerate better than axons in the CNS - Answers the presence of a
perineural sheath in the PNS (which reforms rapidly after injury) allows the concentration of factors
produced by Schwann cells, which guide and promote the regrowth of the distal stump. In the CNS,
microglia and reactive astrocytes form a glial scar, which inhibits axonal regeneration.
Summarize experiments that demonstrate CNS axons are capable of regenerating in a PNS
environment - Answers the experiment sectioned a peripheral nerve and observed regrowth. Then
the nerve was sectioned again, but the distal portion of the nerve was replaced with a section of the
optic nerve. No growth was observed. The optic nerve was sectioned and no growth was observed.
Then the distal portion of the optic nerve was replaced with a transplanted peripheral nerve, and
regrowth of the optic nerve was observed.
Summarize the important role of growth/trophic factors in axon regeneration - Answers growth
factors specific to different tissues promote and guide the regeneration of axons to their correct
targets.
Name the inhibitory molecules found in oligodendrocyte myelin - Answers Nogo-A, OMgp, and MAG
act on the neuronal receptors to activate Rho and ROCK (via the PirB, Nogo-R and p75) which inhibit
axonal growth.
Name the inhibitory molecules found in astrocytic glial scars - Answers CSPG activates Rho and ROCK
(via PTP-Sigma) to inhibit axonal growth.
Summarize experiments that provide evidence for an intrinsic growth program that promotes
regeneration - Answers axons in the spinal cord were lesioned and no regrowth was observed.
Peripheral segments of those same neurons were lesioned several days prior to the spinal cord lesion,
and regeneration was observed in both places.
What occurs during Wallerian degeneration - Answers anterograde degeneration of the axon terminal
(distal to the site of injury).
What occurs during the chromatolytic reaction - Answers Nissl substance (the aggregation of ER and
associated ribosomes) spreads throughout the neurites becoming fragmented. The cell body swells
and the nucleus moves to an eccentric position.
Effects on downstream/postsynaptic neurons - Answers downstream neurons begin to die because
they are not innervated.
Effects on upstream/presynaptic neurons (synaptic stripping, etc.) - Answers presynaptic neurons
retract from the dying neuron and are replaced by processes of glial cells. This decreases synaptic
activity and can impair recovery.
Effects on glial cells (oligodendrocytes, Schwann cells, reactive astrocytes, microglia) - Answers
Schwann cell response in axotomy - Answers will break myelin into small fragments and engulf it, they
also secrete factors to recruit macrophages and stimulate axon regeneration.
Macrophage response to axotomy - Answers help Schwann cells to clear up fragmented myelin.
Oligodendrocyte function in axotomy - Answers cannot dispose of the fragmented myelin and instead
rely on microglia.
Reactive astrocytes - Answers form glial scars in response to axotomy.
Delineate the core pathway that regulates axon degeneration following axon injury in mice - Answers
The enzyme NMNAT2 promotes the conversion of NMN to NAD, which is key for generating ATP and
promoting axonal integrity. NMNAT2 also inhibits SARM1, which is an enzyme that degrades NAD into
NAM. NMNAT2 is transported down the axon from the soma in uninjured axons.
NMNAT2 pathway in damaged axons - Answers NMNAT2 cannot travel down the injured axon, and so
cannot promote the formation of NAD. It also fails to prevent NAD breakdown by SARM1. This leads
to rapid depletion of NAD and cessation of ATP synthesis which increases [Ca2+] and promotes axon
degeneration.
Wlds mutant mechanism - Answers this mutant possesses a mutated NMNAT1 protein, which
mislocalizes to the axon instead of remaining in the nucleus. NMNAT1 degrades more slowly than
NMNAT2, allowing it to sustain [NAD] in the axon, staving off axon degeneration. Effects last for 10-12
days after injury.
SARM1 knockout mechanism - Answers the absence of SARM1 allows [NAD] to persist for a time in
spite of axotomy, delaying axon degeneration.
Axon regeneration in the CNS and PNS - Answers
Explain why axons in the PNS regenerate better than axons in the CNS - Answers the presence of a
perineural sheath in the PNS (which reforms rapidly after injury) allows the concentration of factors
produced by Schwann cells, which guide and promote the regrowth of the distal stump. In the CNS,
microglia and reactive astrocytes form a glial scar, which inhibits axonal regeneration.
Summarize experiments that demonstrate CNS axons are capable of regenerating in a PNS
environment - Answers the experiment sectioned a peripheral nerve and observed regrowth. Then
the nerve was sectioned again, but the distal portion of the nerve was replaced with a section of the
optic nerve. No growth was observed. The optic nerve was sectioned and no growth was observed.
Then the distal portion of the optic nerve was replaced with a transplanted peripheral nerve, and
regrowth of the optic nerve was observed.
Summarize the important role of growth/trophic factors in axon regeneration - Answers growth
factors specific to different tissues promote and guide the regeneration of axons to their correct
targets.
Name the inhibitory molecules found in oligodendrocyte myelin - Answers Nogo-A, OMgp, and MAG
act on the neuronal receptors to activate Rho and ROCK (via the PirB, Nogo-R and p75) which inhibit
axonal growth.
Name the inhibitory molecules found in astrocytic glial scars - Answers CSPG activates Rho and ROCK
(via PTP-Sigma) to inhibit axonal growth.
Summarize experiments that provide evidence for an intrinsic growth program that promotes
regeneration - Answers axons in the spinal cord were lesioned and no regrowth was observed.
Peripheral segments of those same neurons were lesioned several days prior to the spinal cord lesion,
and regeneration was observed in both places.
