Von Bartheld: Regeneration Flashcards
What is the difference between regeneration of neurons in the CNS vs the PNS?
In the PNS, when axons are cut or crushed, they can regenerate their axons an dconnect w their target, and lost function can be restored. In the CNS, axon regeneration is very limited.
What are the 3 key steps required for successful regeneration?
- the cell body must survive
- the injured neuron has to re-grow its axon through the environment *neuron sends out a growth cone and the growing axon must find its target
- the new axon must connect with its original target and establish a functional synaptic connection *the target cell must remain viable
After transection of a nerve fiber the axonal membrane will rapidly seal, and an end swelling, the (blank) forms. Thin (blank) emerge from the growth cone which sense molecular cues in the environment and help to decide which path to choose.
growth cone; filopodia
Axonal injury leads to a characteristic retrograde reaction in the affected neuronal cell bodies. What is thought to cause this?
interruption of retrograde axonal transport of trophic factors from the target
An important component of the cell body response to injury is a change in (blank). Some proteins will be expressed at a higher level, while others will be expressed at a lower level. Proteins involved in functions of mature neurotransmission are generally (blank), while those involved in the regenerative process, such as growth-associated protein (GAP 43), are (blank).
gene expression; reduced; increased
The myelin sheaths (blank) to the cut/crush degenerate, (blank) cells proliferate and phagocytose the degenerating myelin. (blank) invade the site of injury and degeneration and participate in the phagocytosis of old myelin and the distal axon segments.
distal; Schwann; macrophages
Nerve fibers in the distal stumps of lesioned nerves (blank) while those proximal to the injury (blank). The axonal degeneration of the distal stump is called (blank) degeneration. This degeneration is an active destructive process, possibly induced by interruption in the delivery of trophic signals and materials from the cell body. It helps to provide a suitable pathway for successful axonal regeneration.
degenerate; survive; Wallerian
The cut end of the axon sprouts a new growth cone and it grows along the new Schwann cells. The Schwann cells act as a favorable substrate for the growing axons: they express (blank) (NgCAM, laminin) on their surfaces that promote the growth of axons. Ensheathing and glial cells increase the production of (blank) that stimulate axon growth. In large mammals like humans, regeneration is a slow process which takes weeks to months.
CAMs; trophic factors
Schwann cells secrete these to promote the growth of the axon along the pathway to the target. Examples include NGF, BDNF, GDNF, CNTF, FGFs and IGFs. These modulate the regeneration process, and the actions of these trophins depends on the neuronal cell type, expression of receptors, and the stage of regeneration
growth factors
The axons grow back to their targets along (blank). Not all of the axons make it, and they usually do not innervate exactly the original cells in the target. The regenerated axon contacts cells within the target by-and-large (blank). As a result, some of the functional contacts between regenerated axons and their target may not be appropriate. The new axons become myelinated and return to their former caliber. The cell body resumes its normal protein synthesis.
Schwann cells; non-selectively
Which kind of nerve damage, a crushed nerve (with some continuity of endoneurial tubes) or a completely cut nerve, will have more appropriate innervation of original targets?
crushed nerve
Regeneration in the PNS is often successful, but regeneration in the CNS of mammals is minimal. The CNS cell body shows a similar response after axonal injury, so how does regeneration differ in the PNS?
the proximal segment of the axon produces only small, short-lived sprouts;
Wallerian degeneration of distal axon is much slower;
myelin debris blocks the pathway and astrocytes proliferate and form dense astrocytic scars
What happens when damaged CNS neurons are provided with a peripheral nerve graft containing Schwann cells?
some neurons will regenerate their axons and can make functional connections w their former targets
Studies show that the adult CNS fails to provide an appropriate, stimulating environment for axonal regrowth. Studies have shown that (blank) inhibit the growth of regenerating axons and that these CNS glia cells express myelin-associated glycoproteins (such as MAGs and Nogo proteins) which cause growth cone (blank).
oligodendrocytes; collapse
What kinds of things can cause loss of neurons?
injury
toxins
idiopathic reasons (autoimmune, genetic)
Can hair cells in the organ of Corti regenerate?
no :(
*cochlear implants can provide some hope
(blank) cells can be lost after optic nerve trauma, leading to blindness. There are animal models in which trophic factors are applied to the eye to rescue the retinal ganglion cells after optic nerve section and to stimulate regeneration of the axons. Promising trophic factors are BDNF and GDNF.
retinal ganglion
How is nerve degeneration involved in Parkinson’s disease?
dopaminergic neurons of the substantia nigra degenerate in Parkinson’s disease. The degeneration is thought to be due to trophic dysfunctions.
Cholinergic basal forebrain neurons degenerate in (blank), again presumably due to trophic dysfunction. These neurons respond to NGF and other neurotrophins.
Alzheimer’s disease
(blank) degenerate in amyotrophic lateral sclerosis, a disease which leads to death within years.
upper and lower motor neurons
(blank) degenerate in retinitis pigmentosa
photoreceptors
glial cells can also degenerate. In multiple sclerosis, (blank) and their myelin degenerate (demyelination), possibly caused by an autoimmune reaction due to a shared antigen between CNS myelin and an unknown virus
oligodendrocytes
Novel strategies for replacement of lost neurons involve (blank)
stem cells
These cells can be used as grafts in the brains or spinal cords of patients with degenerative diseases to replace the lost neuronal population and their functions.
stem cells
