Lecture 11 - Diseases of the nerve and motor units Flashcards
What are the three major types of muscle?
- smooth
- skeletal
- cardiac
What are the three ways neurological disorder affect movement?
- AP conduction along MN
- synaptic transmission from MN to muscle
- Muscle contraction itself
What four parts of the NMj can be affected?
- cell body of MN - MN disease
- axon of MN - peripheral neuropathy
- NMJ synapse - disorder of NMJ
- muscle fiber - myopathy
What two MN disease where the cell body of the MN is affected were discussed in class?
ALS - can cause pain in extremetiris and muscle to weaken and voice to squeak and freezing - die due to airway death
SMA - found in children born with it
What are the two gene associated with ALS?
- sod1 - scavegnes free radical and prevent oxidative stress and is enzyme in mitochondria
- C9orf72 - GGGGCC expansion causes cytotoxicity causes defects in nuclear pore complex - expansion can cause haploinsufficency - or mRNA toxivity or protein toxivity
What gene is associated in SMA?
SMN1 gene - defective rna splicing and processing
-can inject dsRNA of smn2 to make it more stable so it can do the splicing more
What happened in the SMN mutated mice?
could not breathe or move
What two things can cause a peripheral neuropathy in which the axon of the MN is affected?
- impair in myelination of MN - schwann cell cannot myelinate
- imapir axonal function itself
Apply a shock at S1 or S2 and the longer the latency what happens? - this means the slower the conduction along the peripoherla nerve which indicates peripheral pathiology in the axon myelin
Would have deynshronzied aps if have issue with myelination
What can giver rise to peripheral demyleination?
defects in multiple gene - Tfs, ABC transporter in peroxisomes, genes involved in organizing myelin
How are peripheral axons wrapped in myelin?
so that the axon is compact and tight except near the nodes of ranvier
What defines major dense lines of myelin?
rings of cytoplasm that have myelin basic protein
What are the three myelin associated proteins that are defective in 3 different demyelinating neuropathies?
P0, PMP22, connexin-32
How do genetic defects in intracellualr neuronal proteins cause axonal neuropatheis?
stress to axonal cytoskleeton and axonal transport can be a major trigger for this - i.e. not enough sodium channels can cause not as great an AP via transport defects
What is the NMJ synaptic disease discussed in class?
myasthenia gravis
What happens in myasthenia gravis?
the immune system attacks postsyanptic achr leading to reduces achrs and simplified synaptic folds
If you inject an acetylcholineetserase inhibitor like neostigmine what happens?
myasthenia gravis is better cause more ach in terminal
How does the turnoves of achrs increase in MG?
cause of crosslinkong of asntibodies which cayses endocytosis and destruction of receptotrs and the membrane to lysis
What are the two myopathies discussed in class?
- muscular dystrophy
- myotonia
What happens in muscular dystrophy?
defective protein weakens the muscle membane or slow repair after injury mutation in dystrophin gene in which scaffold that stabilizes structural complexes in muscles
What does dystrophin do?
anchors muscle to ecm and is a scaffold protein
What happens in severe duchenne dystrophy?
deletion of on exon causes stopn codon and severe truncation of gene
What happens in Becker or mild dystrophy?
four exons removed causing a functional but removed segment of protein
What causes myotonia?
impaired inactuvation in sodium channels - no ball longer chain - rapid burst of ap from a single stimulus
What can cause myotoniab or muscle paralysis?
spectrum of voltage gated ion channel channelopathies can cause this
What happens when MNs are diseased?
muscles formerly innervated by cell A become atrophic and adjacent neyron then hyperinnervates them leading to a larger reponse in slight contaction but lower maximal contraction
-frequecny decrease and amplitude increase - cause less muscles are innervated but dome muscle are hyperinnervated so get a huge spike
What happens when the muscle is diseased?
the number of muscle fibers in each motor unit are reduced some shrink and become nonfunctional so the maximal response is reduces and smaller and shirter in duration - same frequecny less amplitude cause less are firing
