Midterm 3 Flashcards
______ is an age-related cognitive decline that reaches a pathological level
Dementia
Alzheimer’s, Parkinson’s, and Huntingtin’s disease are all a form of ______
Dementia
What are the symptoms of Alzheimer’s disease?
Memory: Retrograde amnesia as well as deficits in storing new memories (anterograde amnesia)
Deficits in executive function (complicated tasks with multiple tasks) ex. cooking
Agnosia: failture to recognize objects
Apraxia: impaired motor function
Aphasia: impaired langage function
What is the survival time after diagnosis of AD?
~8 years after diagnosis
Cognitive deterioration is slow during the early and alter stages but quite rapid during the middle stage
As the disease progresses, symptoms become more severe and at the final stage the individual is typically completely dependent on caregivers
What is the progression of AD?
Starts mild absentmindedness and language becomes more simpler and more concrete
As it progresses, language skills decline, LTM deficits occur, affection and emotion become affected (irritable, aggressive, outburst, childlike), and become confused and wander around
What is Anosogonsia?
A lack of awareness that one has Alzheimer’s, often seen in people with mid-stage AD
What is the typical age of onset of AD?
Appears between 60s-70s
Early-onset AD can appear as early as 40s, also known as pre-senile dementia
What is the purpose of long-term potentiation and depression?
It maintains a record of activation - synapses that are frequently stimulated become stronger and easier to stimulate in the future
Neurally, how are brains thought to store memories?
Each unique experience activates a combination of neurons and synapses
Each network or ‘trace’ is unique thus storing a memory
As you experience the same thing over and over, this network becomes stronger, which is how people become good at something
What analogy did Dr. MacKay use for storage of memories?
Walking down a laid pathway in the winter
Each time someone walks on the path, the path becomes worn in, and easier to travel
If you learn something and then during aging a crucial neuron in your circuit or trace dies, what will happen?
Your brain will take an alternative route. The entire circuit is not lost, but it does mean the circuit will work less efficiently
What happens to the brain of someone with AD?
- shrunken cortical gyri,
- reduced gray matter
- massively enlarged ventricles
- increase CSF
What causes neuronal death in AD?
Post-mortem analysis finds increased clusters of amyloid-B plaques
These are neurotoxic and as they accumulate they choke off adjacent neurons, leading to cell death
There are also increased neurofibrillary tangles which are defective neurofibrils that occurs due to an excess of hyperphophorylated Tau proteins
Neurofibrillary tangles occur in the axons
True or False
False
It occurs in the cytoskeleton
How is AD diagnosed?
Using a PET, imaging can quantify amyloid-B in a living brain using radioactive dye
Until recently it was only diagnosed post-mortem
What is the purpose of the cytoskeleton?
It functions as a flexible scaffold that’s solution allows a neuron to maintain their 3D structure
It also transports proteins and molecules across vast distances
What are the 3 main components to the cytoskeleton?
Neurofilaments - control & transport of membrane proteins
Microtubules- control the transfer/movement of substances and organelles through the cytoplasm
Microfilaments - provides structural support to axons & dendrites
What are Tau proteins? What are hyperphoshorylated tau proteins?
Tau proteins are involved in the stabilization and flexibility of microtubules and microfilaments
They are a highly soluble protein that are activated through phosphorylation and promote assembly of microtubules
However, hyperphosphorphyated tau proteins begin to accurate which eventually form neurofibrillary tangles inside cell bodies
Microtubules disintegrate and destroy the cytoskeleton - collapsing the transport system, causing biochemical malfunction, leading to cell death
What is the pattern of neural degeneration in AD patients?
Begins in the frontal, posterior parietal lobe, and temporal lobes and then spreads to other regions
This is why earliest symptoms are cognitive impariemtns, memory loss, and reduced impulse control
The majority of AD cases are inherited
True or False
False.
Twin studies suggest a 40% concordance rate which means there are some genetic component:
- Mutations in the gene coding from amyloid precursor protein (APP) can increase the risk of AD
- Apolipoportein E is another protein involved in the genetic risk
How can chronic stress impact AD patients?
Chronic stress leads to neurodegeneration and increases the build up of amyloid-B plaques
The combination of stress and amyloid-B show impaired memory
What is the treatment of AD?
There is no pharmacological treatment to death with pathology of AD
Medication can only temporarily mitigate some deficits
- Acetylcholinesterase inhibitors increase levels of ACh which is lost in AD patients
- NMDA antagonists block the NMDA glutamate receptors: dying neurons dump excess glutamate which are toxic and can lead to a chain reaction
These treatments do not extend the life of a person with AD but it increases their time before becoming severely impaired
What is ALS?
Amyotrophic Lateral Sclerosis is a progressive degenerative disease that affects neurons controlling voluntary muscles
No muscle nourishment on the spinal cord where sclerosis (scarring/hardening) occurs
ALS is hereditary
True or False
True
Some cases are inherited but there are also sporadic cases
What is the common death in someone diagnosed with ALS?
Respiratory failure 2-4 years after diagnosis
What are the symptoms of ALS?
Loss of motor neuron function result in: stiff muscles, muscle twitching, weakness due to decreased muscle size, difficult speaking, swallowing and breathing (1st symptoms to appear)
People eventually lose the ability to control all voluntary movements
Cognitive dysfunction are present in less than half of cases
What causes ALS?
Results from a degernation of both the upper (motor cortex) and lower (brainstem & spinal cord) motor neurons
The cause of degeneration is unknown in ~95% of cases
Familial cases involve genetic mutations in superoxide dismutase leading to oxidative stress
No specific environmental factors have been identified
Which types of neurons are more susceptible to damage?
long neurons such as lower motor neurons
The ________ is the primary control systemm for precise voluntary movements. Where is it located?
corticospinal tract
It begins in the precentral gyrus (aka primary motor cortex) and crosses to the contralateral side of the body at the level of the medulla a(decussation of the pyramids)
If a person hits their head on the left side of their brain injuring the left motor cortex. What symptoms of injury would you expect to see?
Injuries on the right side of the body since the injury is upward of the desiccation of the pyramids
What types of neurons are located in the primary motor cortex? How do they project throughout the body?
Large projection neurons known as pyramidal neurons that send their axons through the internal capsule (a chokehold for motor neurons)
They then pass through the cerebral peduncle in the midbrain
Then through the pyramids in the medulla and 90% cross over at the decussation of pyramids and 10% stay ipsilateral
The ones that cross over join the lateral corticspinal tract
The ones that do not join the anterior corticospinal tract and then decussate at the spinal cord before they connect with their lower motor neurons
What are the difference between upper and lower motor neurons?
Upper motor neurons (UMN) are pyramidal cells that synapse onto interneurons in the spinal cord and live in the primary motor cortex
Lower motor neurons (LMN) are efferent nerve fibers that carry signals from the spinal cord to the muscles and live in the ventral horns of the spinal cord
What happens at a neuromuscular junction?
It is where the lower motor neurons attach to a striated muscle
The motor neurons release ACh which binds to either nicotinic or muscarinic ACh receptors to cause a muscle contraction
How does botox interact with ACh to cause paralysis?
Botox is taken up selectively by peripheral cholinergic nerve terminals, including those at the neuromuscular junction
Botox interferes with ACh release, blocking the release of ACh from their synaptic vesicles which results in muscle weakness or paralysis
What is the function of acetylcholinesterase?
Acetylcholinesterase is an enzyme that cleans up and disposes of ACh after it has been dumped in the neuromuscular junction
What are nerve agents?
They permanently block acetylcholinesterase which results in a rapid build up of ACh at the neuromuscular junction so the muscles cannot relax and the individual loses complete control of their body
Death occurs by suffocation as you need muscles to breathe
Ex. sarin and VX
What is the motor unit?
The LMN cell body, axon and the multiple fibres it innervates
An AP will depolarize one motor units muscle fibres and multiple APs will overlay each other, leading to larger muscle contractions
What is the pathway involved in starting the shower and determining if the water is hot enough?
- Sensory endings in the skin detect temperature
- AP is sent to the sensory neurons in the dorsal root ganglia
- The sensory axon enters the spinal cord and synapses with a interneuron in the brain (medulla)
- Sensory pathways continues with second neurons projecting to the thalamus
- sensory pathway reaches cerebral cortex
- UMN from the cortex executes a motor command
- UMN connects to a LMN in the spinal cord
- The LMN causes contraction of the target skeletal muscle
What are the pathways of an afferent sensory input?
The afferent sensory sobers enter the dorsal root bringing sensory info from the receptors
They then go 1 of 3 ways:
- Directly to the CNS
- Synapse with LMN to elect an immediate response
- Synapse with an interneuron
Why are reflexes tested?
Simple reflex tests can help identify damage to the upper or lower motor neurons
Ex. A weakened/absent knee jerk reflex indicates LMN damage; an exaggerated knee jerk indicates UMN damage
What is the pathophysiology of ALS?
ALS has an increased presence of inclusion bodies in the cytoplasm of motor neurons. Aggregations lead to dysfunctional motor units and cause cell death
Which proteins aggregate differ depending on the type of ALS (sporadic vs. familial)
How is SOD involved in ALS?
superoxide dismutase (SOD is an enzyme that catalyzes the disputation of the superoxide radical (O2-) into a less toxic chemical
If not regulated, O2- can cause many types of cell damage
People with familial ALS have disruptions in SOD1 functioning causing O2- levels to rise
How is ALS diagnosed?
Based on patient history, neurological exams (reflexes), and EMG testing
Muscle injuries results in smaller motor unit potential measures (EMG) ; injury to axons result in larger motor unit potentials
What is the treatment of ALS?
There is no cure for ALS
Riluzole, an anti-glutaminergic drug, may extend life expectancy and QoL by preventing excitotoxicity caused by increased Ca2+ due to excessive release of glutamate
Contrast nociceptive and neuropathic pain
Nociceptive pain arises from tissue damage (adaptive)
Neuropathic pain arises from damage to the damage-reporting system in the nervous system
How do we perceive pain?
- A nociceptor is a sensory neuron that responds to damaging stimuli by sending possible threat signals to the spinal cord where it synapses with a secondary neuron in the dorsal horn
- This neuron crosses to the contralateral side where it travels through the medulla to the thalamus where in synapses and passes through the internal capsule
- The signals is then sent to the sensory cortex in the parietal lobe
- If the brain perceives this signal as a threat, it will create the sensation of pain and initiate a cascade of events to deal with it (known as nocicpetion)
What is the dorsal columns tract?
It is used for precise fast information in the cuneatus and gracilias nucleus
What is the difference between free nerve an encapsulated nerve endings?
Free nerve endings are embedded in tissues
Encapsulated nerve endings synapse with tissues
What is the difference between afferent and efferent signals?
Afferent is incoming - they come through the dorsal horns
Efferent is outgoing - they come through the ventral horns
DAVE - Dorsal Afferent, Ventral Efferent
What are the different types of afferent fibres?
C Fibres: small unmyelinated fibres that carry nociceptive info
ABeta, ADelta Fibres: medium, myelinated fibres that carry nociceptive and non-nocicpetive info
Alpha Fibres: large myelinated fibres that carry light touch and proprioception info
What are the different types of pain?
Somatic pain refers to localized injury to skin, muscles, bones, joints, and connective tissues (outside); fast and slow pain (A and C fibers)
Visceral pain refers to poorly localized pain that results from the nociceptors of internal cavities such as thoracic, pelvic, or abdominal viscera; slow pain only (C fibers)
Which structures in the CNS respond to pain?
Dorsal horn - site where pain is modulated and afferent fibers are sent to thalamus
Sensory homunculus - in the somatosensory cortex where we consciously perceive localized pain
Limbic system - Emotional arousal
Midbrain - Autonomic activation (increased HR, BP)
In response to pain what does gating refer to?
Gating is one way in which humans modulate pain
The gate theory suggests that non-painful stimuli close the ‘gates’ to painful input which prevents pain sensation from travelling to the brain
Ex. shaking your hand after you hit with a hammer
There is a projection neuron in the dorsal horn: C-fibers send a pain signal and ABeta fibers send proprioception info to that projection neuron
However, if the ABeta fibers send a signal at the same time as the C fibers the ABeta fibers activate an inhibitory neuron which inhibits the signal of the pain (closing the gate)
How does the brain modulate pain (top down influence)?
The brain will activate descending neural pathways to dampen afferent signals in response to pain stimulus
Starts in the periaqueductal gray matter -> Medulla -> spinal cord -> synapse with secondary neurons in the dorsal horn and inhibit firing of afferent neurons
This occurs due to 5-HT, NE, cannabinoids and opioids
What is inflammation?
Inflammation is a localized physical condition in which the body becomes reddened, swollen, hot and often painful
It occurs due to the release pro-inflammatory cytokines =, it makes peripheral nerves, dorsal horn, and thalamus/somatosensory cortex more excitable
These are ongoing processes which up regulate pain
What is sensitization?
When your pain is unregulated due to:
An increase # of glutamate receptors, making post-synaptic membranes are hyper excitable and now, even normal stimulus will be perceived as noxious
Broken/damaged cells release pro-inflammatory cytokines (prostaglandin, bradykinins) that up regulate receptors leading to hyper excitability and CNS sensitization
Hyperalgesia occurs when a slightly painful stimulus is very painful due to the hyperactiation of peripheral nerve fibers (overactive C-Fibers)
Allodynia occurs when a stimulus that should not be painful is painful due to A-fibers send inaccurate signals
How do NSAIDs work?
They inhibit the production of prostaglandin to stop inflammatory cascade
What are the cogntive inhibiting and sensitizing factors to pain?
Inhibiting:
- anticipation of relief from pain
- distraction
- positive outlook
- cognitive contextualization of stimulus
Sensitizing:
- expectation of pain
- attention to pain
- depression/anxiety
- lack of understanding or context for stimulus
What typically causes neuropathic pain?
Since it is not due to injury it is typically caused by an up regulation or dysfunctional ion channels (Na channels) which can lead to hyper excitability and cause painful signals in absence of injury
How is pain managed?
Pharmacological agents:
- locally acting agents: local anaesthetics (blocking neurons), topical NSAIDs
- Non-opiates: COX inhibitors, acetaminophen, neuropathic agents, cannabinoids, antidepressants
- Opiates: codeine, morphine, hydromorphone, fentanyl, methadone
Non-pharmacological:
- Local: fixation of tissue (pressure), surgical excision, physio/massage therapy, hot/cold compress, exercise
- Central: psychological support, stress management, distraction, DBS, exercise, physio
What is PTSD?
A mental health disorder that develops after a traumatic experience
It is thought to be a disturbance of memories and is characterized as a stress response that won’t turn off
PTSD is more common in women
True or False
True
Which type of trauma is more likely to result in PTSD?
Interpersonal trauma (e.g., sexual assault)
What are symptoms of PTSD?
Symptoms are likely to arise up to a year after the event and include:
- Anxiety, intrusive memories, dreams/flashbacks, irritability, poor impulse control, social isolation, emotional numbness
- Patients with PTSD will attempt to avoid and trauma-related cues/triggers
How are flashbacks triggered?
They are triggered automatically by situations that reflect aspects of the traumatic event
E.g. noise of an ambulance activates a response that leads to re-experiencing of intrusive event
How is PTSD diagnosed?
It is a DSM-5 disorder
Diagnosis requires exposure to traumatic event along with:
- Event is persistently re-experienced in memories, nightmares, flashbacks, etc.
- Avoidance of trauma-related stimuli
- Negative thoughts/feelings that began or worsened after the events
- Trauma-related arousal and reactivity
- Symptoms must last longer than 1 month
