Lecture 6 Flashcards
neuron
primary communication/information cell type of the nervous system
glial cells
supportive cells of the nervous system
neuron structures
cell body (soma)
dendrite
axon
terminal axon
neuron function
responsible for neurotransmitter signaling in the nervous system
cell body
production factory for all components of the neuron: enzymes, proteins, membrane structures, organelles
cell body clinical application
abnormal protein synthesis, assembly and clearance associated with neurodegenerative diseases
dendrites
sensory input
narrowed extension of cell body that results in huge synaptic surface area - 30x’s surface area of cell body
axons
conduct action potentials for signaling
myelinated= nodes of ranvier: located between myelin sheaths allow faster transmission of action potential, internode: segment that is covered in myelin
unmyelinated = slower transmission of AP
anterogade transport
cell body to terminal axon
retrograde transport
terminal axon to cell body
microtubular highway
transports molecular components necessary for cell function and structure
consists of microtubules and neurofilaments
microtubules
hollow tubes made of protein molecules
motor proteins
transport cellular substances to/from cell body along the microtubule
terminal axon and synapse
neurotransmitter synapse with a dendrite
terminal axon releases neurotransmitter -> terminal end is responsible for re-uptake of neurotransmitter -> neurotransmitter is broken down/recycles in terminal axon
presynaptic side
contains synaptic vesicles filled with neurotransmitters -> AP signals calcium influx to facilitate neurotransmitter release -> also responsible for re-uptake of neurotransmitter from synaptic cleft
post synaptic side
target dendrite or cell
neurotransmitters binds to receptors (proteins) -> after recognized by post-synaptic receptor is released back into the synaptic cleft
types of glial cells
astrocytes
oligodendrocytes
microglial cells (microglia)
ependymal cells
schwann
astrocytes
fill the space between neurons
dynamic and significant role in CNS signaling, function and health
damage/dysfunction leads to CNS pathology
astrocytes processes
surround the blood vessels in the brain/CNS
form synapses with other neurons and other glial cells
astrocyte functions
regulate the BBB
transport nutrients = rapid removal of excess glutamate, maintain extracellular potassium
regulates synapses
remodeling = neuron recovery and scar formation after neuron injury
gliosis
glial cell reaction or responses to CNS injury/damage
astrogliosis
reactive defense response that minimizes/repairs damage to the CNS and plays a role in scar formation
astrocyte dysfunction
acute injury/trauma/stroke
neurodegenerative diseases: Alzheimer’s, Parkinson’s, MS
psychiatric: disrupted signaling
oligodendrocytes function
myelinating axons of the CNS
oligodendrocytes pathology
there will be demyelination
microglial cells function
clear toxic materials
ependymal cells
specialized epithelial cells that line the ventricles, central canal of the spinal cord, and choroid plexus of the CNS
schwann cells function
only in PNS
responsible for myelinating axons in the nerves of the PNS
also provide connective tissue support and have a phagocytosis role in the peripheral nerve
proteinopathies
develop from abnormal protein production or excess accumulation of cellular proteins within and/or around neurons
excess accumulation of proteins eventually leads to neuron cell death
different types of proteinopathies
α-synuclein
Tau protein
beta amyloid plaque
TDP-43
neurodegenerative disease
Alzheimer, pick’s disease, chronic traumatic encephalopathy (CTE), Huntington, Parkinson, Lewy body dementia, ALS
Alzheimer
α-synuclein
Tau protein
beta amyloid plaque
Pick’s disease
Tau proteins (Pick bodies)
chronic traumatic encephalopathy (CTE)
Tau proteins
Parkinson’s disease
α-synuclein
Alzheimer’s disease
progressive onset of symptoms that range from small memory loss to severe memory loss, cognitive loss, and personality changes
*most common form of memory loss
*prevalence increases with age
Alzheimer’s pathology
progressive widespread atrophy of the cerebral cortex
*begins in the temporal lobe
astrocyte dysfunction=disrupted glutamine and protein clearance, reduction of blood flow and damage to BBB
proteinopathy= impaired protein clearance and abnormal protein accumulation leading to formation of neuritic plaques, neurofibrillary tangles
neuritic plaques (amyloid plaques)
abnormal accumulation of beta amyloid
healthy CNS = protein constantly produced from cell membrane and removed from the brain
alzheimer’s CNS = promotes excess amyloid and accumulation of beta amyloid proteins form neuritic plaques that surround and damage axon
intracellular protein accumulation
neurofibrillary tangles
abnormal accumulation of Tau proteins within the axon forming neurofibrillary tangles
healthy CNS = tau proteins equilibrium are regulated by phosphorylation of Tau proteins
alzheimer’s CNS = excess tau phosphorylation disrupts the microtubule structure/function causing abnormal tau protein accumulation creating neurofibrillary tangles
extracellular protein accumulation
trauma and AD
traumatic brain injury can increase risk of developing alzheimer’s disease
trauma disrupts cell function, causes abnormal protein clearance pathways and may form a proteinopathy that leads to Alzheimer’s disease
Alzheimer’s Disease: Clinical Features
visuospatial deficits
memory deficits
impairment with planning and performing familiar tasks
judgement, safety, and a problem solving impairments
personality changes
language decline
motor impairments = posture, gait, bradykinesia
Pick’s Disease
frontotemporal dementia (FTD)
Pick Body Dementia
Pick’s Disease: Signs and Symptoms
apathy
poor insight into consequences of behavior
repetitive behaviors
loss of personal hygiene
loss of social graces
impulsive behaviors
disinhibition
Pick’s Disease Pathology
mutations of the tau gene causing abnormal Tau protein accumulation that lead to neuron death
pick’s disease neurofibrillary tangles are round (Pick bodies)
Multiple Sclerosis
demyelinating disease that damaged oligodendrocytes and disrupts the nerve signaling
UMNL
location: injury to the CNS
muscle tone: hypertonia
reflexes: hyperreflexia, + Babinski
weakness: spastic paralysis
atrophy: slow/disuse atrophy
LMNL
location: injury to the PNS
muscle tone: hypotonia
reflexes: hyporeflexia, - Babinski
weakness: flaccid paralysis
atrophy: quick atrophy
MS pathology
impairment of BBB/astrocytes
promote inflammation responses that target oligodendrocytes and cause damage to the myelin sheath and potentially the axons of the CNS neurons
episodes of acute inflammation = MS flare
MS proteinopathy
MS plaques (scarring) develop from prolonged or severe episodes of immune/inflammation attacks
astrogliosis = reactive defense response and scar formation in immune/inflammation attack
fibrous scars (plaques) replace may permanently damaged neurons
TDP-43
synaptic protein bassoon (Bsn) proteinopathy
MS: Exacerbations
vary in frequency and duration
triggers may include = viral or bacterial infections, stress, heat, poor health
acute concussion
absence of gross CNS damage = result is a functional loss and not structural damage
neurological imaging = no structural abnormalities are demonstrated in standard neurological imaging studies
acute concussion pathology
- initial injury causes transient microscopic disruption “neuron gets dinged” = stretch/deform the cell membrane, alter axonal transport, abnormal neurotransmitter glutamate release and electrolyte imbalance
- astrocytes work overtime and are unable to maintain CNS homeostasis from the excess release of intracellular and extracellular glutamate, potassium, calcium, and glucose
- mismatch of cerebral blood flow is inadequate for metabolic demands of the jolted neurons = astrocytes are unable to maintain adequate blood flow to the area
Chronic Traumatic Encephalopathy
progressive neurodegenerative pathology associated with any form of repetitive mind brain trauma
symptoms of CTE
memory loss, depression, suicidal, aggressive affect, cognitive loss and sometimes motor impairments
CTE pathology
repetitive trauma disrupts protein clearance pathways
CTE proteinopathy
abnormal accumulation of tau proteins form neurofibrillary tangles, similar to AD but has a different regional distribution pattern in the brain
does NOT have amyloid accumulation
CTE often not diagnosed until after death = no current diagnostic markers for living individuals
structure of peripheral nerve
epineurium = outer most layer, surrounds one peripheral nerve
perineurium = surrounds one fascicle or group of nerve bundles
endoneurium = surrounds a single axon
schwann cells
specialized glial cells located only in the PNS
function = myelinating axons in the nerve of the PNS, also provide connective tissue support and have a phagocytosis role in the peripheral nerve
mechanism of injuries to peripheral nerves
stretch/traction force injuries
laceration injuries
compressive force injuries (entrapment neuropathies)
wallerian degeneration
process of degeneration that provides opportunity for regeneration to occur
phase 1 = acute nerve injury
phase 2 = degeneration (immune response)
phase 3 = regeneration
neuropraxia
least severe nerve injury with good prognosis
focal demyelination, but no axonal loss
wallerian degeneration does not occur
complete recovery in 3 to 6 weeks
axonotmesis
variable severity nerve injury
disruption of axons with perineurium and epineurium remaining intact
wallerian degeneration occurs
variable progress and may require many months
neurotmesis
most severe nerve injury
complete transection of all components of the nerve
wallerian degeneration occurs
requires surgical repair or no chance for improvement
peripheral nerve recovery
rate of recovery = slow
1-2mm/day
0.04 to 0.08 inches per day
1 - 2 inches per month
motor recovery = approximate window of 12-18 months before irreversible motor end plate degeneration occurs
sensory recovery = time frame for sensory reinnervation is longer than motor but eventually plateaus/stops
