Nervous System Flashcards
Why is the generation of electrical signals such a central part of our ability to act/carry out task in the world?
Our ability to conduct ourselves in the world is highly dependent on our ability to move which relies on musclar contraction - hence, given that the signals that co-ordinates movement are electrical in nature (neuronal communication), these electrical signals play a central role in our existence
Therefore, we can see that disruption of this system can lead to negative health outcomes.
What is amyotrophic lateral sclerosis (ALS)?
ALS is a motor neuron disease
- Progressive degeneration of upper and lower motor neurons
Upper motor neurons – descend down from cortex into spine
Lower motor neurons – spine to periphery -control activation of skeletal muscles - Signals required for movement of the muscles and their contorl are disrupted
- Inability to initiate and control voluntary movements
- Eventually leads to inability to speak, eat, move and eventually breathe
- ALS does not affect brain function (cognition, sensory perception etc)
- There is no known cure for ALS - mortality is 100%
Outline the disease progression for ALS.
Risk factor - head impact
Early symptoms - Slight weakness and tingling in the hands and limbs (early symptoms)
As the disease progresses (weeks to months):
- twitching & cramping of the muscles
- loss of motor control hands & legs
- tripping & increased incidence of falling
- persistent fatigue
- slurred speech
Late stage symptoms (>1 year):
- Difficulty breathing
- Difficulty swallowing
- Paralysis
Average life expectancy after diagnosis 2-5 years.
What do we know so far about ALS disease mechanism?
Disease mechanisms
- Exact cause of the disease is unknown
- Genetic mutations & environmental factors have equal importance
- 20 genes have been associated with ALS (SOD1, C9orf72..)
- Genetic dysfunction leads to protein aggregation in upper and lower motor neurons - proteinopathy
- Neuronal dysfunction & cell death drive main ALS symptoms
What is multiple sclerosis? What are the associated symptoms?
MS is a demyelinating disease that affects the conduction of electrical signals in the CNS - autoimmune disease
Commonly develops & is diagnosed in patients in their 20s or 30s
Causes a wide range of symptoms (blurred vision, uncontrolled voluntary movement, loss of sensation & balance)
Average life expectancy is only slightly reduced and symptoms can be managed - less severe than ALS
Outline the disease progression for multiple sclerosis?
The different stages include…
- Clinically isolated syndrome (CIS) - first episode that causes inflammation & damage to nerves (myelin)
- Relapsing-remitting MS (RRMS) - follows a predictable pattern where symptoms worsen and then improve (relapse and remission - oscillation)
- Secondary-progressive MS (SPMS) - RRMS can develop into a more aggressive and progressive form of the disease if left untreated - more advanced/severe form - cumulative negative impacts on neurons
On a cellular level what does the pathophysiology of MS look like?
Main characteristics
1. Formation of lesions in the CNS (called plaques)
2. Inflammation due to autoimmune response
3. Destruction of myelin
Combined effects: disrupted signalling between neurons in the CNS, leading to blurred vision, uncontrolled voluntary movement, loss of sensation & balance etc
Describe the socioeconomic burden caused by ALS?
- Estimated 250,000 cases worldwide
- Affects people of all races & ethnic backgrounds
- Military veterans 1.5-2 times more likely to develop ALS - reasons unknown, could reflect exposure to lead, pesticides & toxins
Annual costs:
€78K per patient / year
€250K per patient lifetime
High costs due to the requirement of 24-hour care in the latter stages of the disease
What are the current treatment strategies of ALS?
Incurable neurodegenerative disease
Life expectancy after diagnosis 2-5 years
Main treatment strategy is symptom management:
- physical, occupational, speech & respiratory therapies
- exercise in moderation
- hot sauna/steam rooms to relax muscles – some patients report constant contraction
FDA approved drug - ‘riluzole/rilutek’
1st drug to prolong survival
by 2-3 months
Why are there no/limited number of treatments for ALS?
Limited understanding of pathophysiology - making it difficult to create treatments
Limited understanding of the genetic origins and environmental factors –> hence, resulting in a reduced capacity to design drugs & target therapies
Hence, we need to develop a deeper understanding of disease mechanisms so that entry points for therapeutic interventions can be created.
Desrcibe the socioeconomic burden of MS?
Estimated 2.5 million cases worldwide
~130,000 in the UK alone
Affects people of all races & ethnic backgrounds
Identical twins share the same genetic makeup, but the risk for an identical twin is only 1 in 4 - highlights the importance of environmental factors
Annual costs:
£10-40K per patient / year depending on severity
£0.4M - £1.6M per patient lifetime - overall larger cost as the patients are able to live for longer
Differing levels of home care depending on severity
What are the current treatment strategies for MS?
No cure, symptom management - reduce number of relapses and accumulative damage
- Focus on managing relapses (avoiding nerve damage due to inflammation) via…
a) corticosteroids reduce inflammation
b) plasmapheresis (plasma exchange)
Disease modifying treatments (DMTs)
variety of approved drugs available
- Betaseron, Avonex, Copaxone…. all drugs reduce relapses & inflammation
Aslo consider rehabilitation - exercise programme to address physical challenges associated with MS
Psychosocial support - chronic, debilitating disease can affect mental health, support groups provide support structure
Why are there a limited number of treatments available for MS?
- Disease modifying treatments are available and slow disease progression, but efficacy varies (significant side effects)
- Limited understanding of the genetic origins and environmental factors - makes it hard to develop effective therapeutics
- Require a deeper understanding of disease mechanisms to provide entry points for therapeutic interventions
What was the neuron doctrine prosposed by Santiago-Ramon y Cajal?
Law of Dynamic Polarisation - preferred direction for cell-to-cell communication - neurons send information in a unidirectional manner (from dendrites to axons) –> holds true
What are the different compartments of a neuron?
Note - Cell body or soma
What are the three categories of specialised glial cells present in the nervous system?
Astrocytes:
- Most numerous cells in the brain
- Fill spaces between neurons
- Regulate the chemical content of the extracellular space
Schwann cells:
- oligodendroglial cells - CNS
- Schwann cells - PNS
- provide myelination of axons
Microglia
- brain’s resident immune cell
What are the two main divisions in of the nervous system?
Central Nervous System (C.N.S)
- brain and spinal cord
Peripheral Nervous System (P.N.S)
- long axons radiate from C.N.S to innervate the rest of the body
- sensory (afferent) axons take information from the periphery to the C.N.S
- motor (efferent) axons convey information from the C.N.S to muscles
What are the dorsal and ventral roots? What types neurons do they have?
Refers to the two main neuronal bundles that exit/enter the spinal cord into the periphery
- Dorsal roots contain afferent axons - send information to the spinal cord
- Ventral roots contain efferent axons - neurons that innervate muscles
- Spinal nerves contain a mix of afferent and efferent axons
What are some activities/actions controlled by the brain and spinal cord?
The brain: cognition, motivation, emotion, learning & memory, volitional movement
Spinal cord: reflexive actions which are automatic, short-latency responses to stimuli, which does not require the brain.
What are the three general functions that electrical excitable are used for?
Excitable cells are electrically charged and use electrical currents to:
- Sense stimuli (e.g. chemicals, pressure, pain, touch)
- Transmit information to each other often over long distances
- Do something (e.g. contract a muscle fibre, release messenger molecules like hormones or neurotransmitters)
What is the basis of electrical excitability of cells?
Since all living systems exist in a water environment
Electrical currents in biology are driven by the movement of ions in solution –> used to generate current
The main ions of interest are: Na+, K+, Cl- & Ca2+
Given that the phospholipid membrane is impermeable to ions, what are the two ways of transport across?
There are only two ways that ions can move across the cell membrane:
- Through ion pumps - active pumping
- Through ion channels - allow free passage of ions down concentration gradient
In a neuron at resting potential, what is the charge across the membrane and what does the ion distribution look like?
Resting potential is roughly -67mV –> means that the inside is more negatively charged relative to the outside
Ions located extracellularly - High Na+ & High Cl-
Ions located intracellularly - High K+ + presence of negatively charged proteins inside the cell
What is one of the main pumps responsible for re-establishing the resting potential ion concentrations?
Sodium-potassium ATPase (Na+/K+ pump)
Na+/K+ pump transfers 3 Na+ ions from inside the cell to outside & simultaneously takes 2 K+ ions from outside and transfers into cell - ATP dependent