NeuroPhys Unit 2

  1. Formation of the nervous system
    • 1) Tissue forms neural tube
    • -Begins as a flat disk = neural plate
    • -Three distinct layers
    • --Endoderm, Mesoderm, Ectoderm
    • 2) Brain formation begins when ends of neural tube close
  2. Neural plate
    Thickening of ectoderm on surface of embryo
  3. Neural groove
    Edges of plate fold and edges grow toward each other
  4. Neural tube
    • When folds touch; cervical region 1st
    • "zips" closed rostrally and caudally, open ends=neuropores
    • -Becomes spinal cord
  5. Neural crest
    • Cells adjacent to neural tube that separate from tube and ectoderm
    • -Becomes the PNS
    • When crest is developed, tube and crest move inside the embryo
  6. Stages of cellular development
    • 1) Cell proliferation
    • 2) Cell migration
    • 3) Cell differentiation
    • 4) Axon extension to targets
    • -Axonal growth
    • -Fasciculation
    • -Axon growth
    • 5) Synapse formation
    • 6) Synapse elemination
    • 7) Synaptic capacity
    • 8) Synaptic rearrangement
    • 9) Hebbian modification
    • 10) Apoptosis
  7. Zones of the neural tube
    • Ventricular zone
    • Cells undergoing DNA replication and division
    • Neurons and some glial cells
    • Lining of ventricles
    • Formed 1st
    • Marginal zone
    • Processes of cells in ventricular but do not contain their nuclei
    • Almost no cell bodies
    • Formed 2nd
    • Intermediate zone
    • Between ventricular and marginal
    • Formed last
    • Cells migrate here from ventricular zone
  8. Cell Proliferation
    • Cell in ventricular zone extends a process up to pia
    • Nucleus of cell migrates up toward pial surface (outer edge of Marginal Zone) and DNA is copied
    • Nucleus, with 2 complete copies of genetic instructions, settles back to surface (of Ventricular Zone)
    • Cell retracts its process from pial surface
    • Cell divides in two = two new daughter cells
  9. Cell/Neuron migration
    • Migrate to final location
    • -Send slender process to brain surface and hoist selves along
    • -Climb along radial glia
    • *Cortex formed "inside-out"
    • *Neurons differentiate after reaching final location; function depends on area of brain
  10. Cell/Neuron differentiation
    • Newly generated cell take on appearance and characteristics of a neuron
    • -Neuronal differentiation occurs first
    • -Followed by astrocyte differentiation
    • -Then oligodendrocyte differentiation
  11. Axonal growth
    • The growth cone
    • -Samples environment and searches for chemical cues
  12. Fasciculation
    Axons growing together stick together
  13. Axon guidance
    • Chemoattractant
    • -Netrin = a protein that attracts neurons in spinal cord to cross the midline
    • Chemorepellent
    • -Robo = a protein that repels the axon to grow away from the midline
  14. Synapse formation
    Agrin molecules 'mark the spot'
  15. Synapse elimination
    • Initially, each muscle receives input from several alpha motor neurons 
    • During development, all but one are lost
    • One to one relationship est.
  16. Synaptic capacity
    Space for only a finite number of synapses
  17. Synaptic rearrangement
    • Segregation
    • Convergence
  18. Hebbian Modification
    • Synaptic plasticity
    • -Changing from one pattern to another
    • -Synaptic competition causes modification
    • -"Neurons that fire together, wire together"
  19. Neurogenesis in the adult neocortex
    • New cells are born in the ventricular zone
    • Migrate through the white matter to the cortex
    • Found in the association areas of the temporal and frontal lobes
  20. Spina Bifida
    • "split spine"
    • Defect of neural tube where portion fails to form or close
    • -Results in defects in the spinal cord or vertebrae
    • Level of protrusion correlates with fetus's neurological, motor and sensory deficits
  21. Spina Bifida pathology
    • No definitive known cause
    • Environmental and genetic factors
    • -Race (whites and hispanics)
    • -Family history
    • -Folate deficiency
    • -Some medications
    • --anti-seize medications during pregnancy
    • -Diabetes, obesity
  22. Occult Spinal Dysraphism (OSD)
    • Aka Tethered cord syndrome (TCS)
    • Form of Spina Bifida
    • Infant born with small dimple in back
    • Other signs include small tufts of hair, red marks, hyper pigmented patches, or small lumps
    • Often located near S1 and S2
    • Spinal cord may not grow the right way as a child ages and result in damage
    • Common sx: bladder/bowel incontinence, asymmetrical leg/feet length, back pain
  23. Spina Bifida Occulta
    • "Hidden" Spina Bifida
    • Mildest and most common form
    • Small gap in spine with no sac protruding
    • Layer of skin covers the opening to the vertebral column
    • Usually no disabilities or symptoms
  24. Meningocele
    • Form of Spina Bifida
    • Sac of fluid comes through the vertebrae but spinal cord does not
    • Spinal fluid and meninges protrude through vertebral opening
    • Typically no nerves are damaged
    • Minor disabilities may occur
  25. Myelomeningocele
    • Form of Spina Bifida
    • Most severe
    • Sac of fluid containing parts of spinal cord and nerves come through opening in spine causing nerve damage
    • Moderate to severe disabilities
    • -70-90% also have hydrocephalus
  26. Physical characteristics of Spina Bifida
    • Sensory loss in legs, feet, or arms
    • Decreased strength/paralysis
    • Increased spasticity
    • Lethargy
    • Bowel and bladder dysfunction
    • Vision problems
    • Scoliosis
    • Speech
    • Renal, cardiac, and orthopedic deformities
    • Clubfoot
  27. Spina Bifida cognitive impairments
    • Most are of normal intelligence
    • Some have learning disabilities
    • Academic ability
    • Verbal memory
    • Perception
  28. Fetal Alcohol Syndrome (FAS)
    • Alcohol crosses the placenta
    • -Baby's BAC is equal to mothers
    • -Amniotic fluid prolongs exposure to alcohol
    • Alcohol alters development in the womb
    • -Interferes with delivery of oxygen and nutrients
    • -Disrupt cell differentiation and growth
    • -Interrupt DNA and protein synthesis
    • -Decreased migration of cells
    • Irreversible changes to fetus
  29. Fetal Alcohol Syndrome clinical features
    • Birth defects
    • -Structural -> microcephaly; deformed brain structures
    • Respiratory complications
    • Renal and genital malformations
    • Cardiac malformations
    • Orthopedic anomalies
    • Neurological/CNS
    • Functional
  30. Facial features of FAS
    • Small eyes with drooping upper lids
    • Short upturned nose
    • Flattened maxilla/cheeks
    • Small jaw
    • Thin upper lip
    • Elongated midface
    • Microcephaly
    • Smooth philtrum
  31. Autism spectrum disorder types
    • Autism
    • Childhood Disintegrative Disorder
    • -A marked regression with multiple areas of functioning after a period of at least two years of normal development
    • Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS)
    • -Exhibits some of symptoms of autism but not all of the symptoms
    • -"Catch all" category for those who don't fit in other disorders
    • Asperger Syndrome
    • -Sometimes considered mild form of autism, but NO language delays, cognitive development delays, or delays in developing self-help skills and environment curiosity
  32. Autism brain abnormalities
    • Abnormal cellular configuration/neural structure
    • Underdev. of amygdala and hippocampus which are responsible for emotion, sensory input, and learning
    • Deficiency of Purkinje cells in the cerebellum = output from cerebellar cortex
    • Vermal lobules Vl and Vll in cerebellum are smaller or larger then normal
    • Abnormalities of several regions of brain including frontal/temporal lobes and the cerebellum
    • More neurons present in select divisions of the prefrontal cortex
    • Abnormal biochemistry
    • Elevated levels of serotonin, glutamate, and/or acetylcholine in the blood and cerebral spinal fluid
    • Elevated levels of beta-endorphins which increases pain tolerance
  33. Autism possible causes
    • Neurotoxicity
    • -Lead, mercury, manganese, pesticides, rubella, inflammatory cytokines
    • Medical conditions
    • -Fragile X, congenital rubella syndrome
    • Combination of genetics and environment
  34. Autism and neural connectivity
    • Connectivity density differs from typically developing brain
    • Hypo of hyper connectivity presence as a predictor of severity of symptoms
    • Extended CNS inflammatory response, activated microglia and inflammatory mediators damage synaptic connections and cause neuronal cell death
  35. Clinical features of autism
    • Social/emotional funtioning
    • -eye contact, facial gestures, relationships, no shared interests
    • Communication
    • -Speech delay or absence, inappropriate social uses of language, echolia
    • Behavior
    • -Intense restricted interests, strictly prefer routines, repetitive motor mannerisms, non-specific motor abnormalities
    • Sensory problems
    • -Highly sensitive
  36. Prognosis of autism
    • Begins before 3 years old
    • -Almost 1/2 saw signs by 12 months
    • -80-90% saw signs by 24 months
    • No cure
    • Early identification = better outcomes 
    • Co-morbities (mental retardation, etc.) = poorer outcomes
    • Severity of manifestations affect outcomes
  37. Chiari Malformation
    • Structural defects in cerebellum
    • Part of cerebellum located below foramen magnum (instead of above)
    • Possibly hereditary
    • Most cases are congenital
  38. Chiari Malformation types
    • Type l - most common
    • Extension of cerebellar tonsils into foramen magnum
    • Type ll - classic CM
    • Extension of cerebellar and brain stem tissue into foramen magnum
    • Myelomeningocele
    • Type lll - most serious
    • Cerebellum and brainstem herniated into the spinal cord
    • Type lV - incomplete/underdeveloped cerebellum
    • Cerebellar hypoplasia
    • -Parts of cerebellum are missing
    • Type O - under debate
    • No protrusion of cerebellum, but CM symptoms present
  39. Features of Chiari Malformation
    • Hydrocephalus
    • -Build up of CSF
    • Syringomyelia
    • -Fluid accumulation in spinal canal -> Cyst formation
  40. Chiari Malformation treatment
    • Asymptomatic: regular MRIs to monitor 
    • Mild symptoms: headache and pain medication
    • Severe symptoms: surgery
  41. Chiari malformation prognosis
    • l: not curable, but treatable and rarely fatal
    • ll: can be fatal for infants/children
    • lll: increased early mortality or severe neurological deficits 
    • lV: high infancy mortality
  42. Neurological Aspects of ADHD
    • Overall decrease in brain volume
    • Smaller corpus callosum
    • Decreased volume in basal ganglia
    • Brian regions involved
    • Frontal
    • Prefrontal - decreased volume
    • Parietal lobe
    • Cerebellum - decreased volume
  43. Clinical features of ADHD
    • Present before the age of 12
    • Chronic
    • Inattentive symptoms
    • Hyperactivity/impulsivity symptoms
  44. Cerebral Palsy
    • Damage to CNS (prenatally, perinatally, or postnatally)
    • Causes
    • Most often due to loss of oxygen to the brain during dev. or infancy
    • Others include infection and metabolic abnormalities
    • Brain damage is usually hypoxic or ischemic and leads to atrophy and necrosis of brain
  45. Cerebral Palsy Sub-Types
    • Spastic
    • Damage to pyramidal tracts, motor cortex, or genital cortical damage
    • Hyperreflexia, spasticity, spastic diplegia, hemiplegia, or quadriplegia
    • Dyskinetic
    • Damage to extrapyramidal tract, basal nuclei, or cranial nerve
    • Athetoid or choreiform movements, loss of coordination with fine movements, facial grimaces, fluctuating muscle tone
    • Ataxic
    • Damage to cerebellum
    • Loss of balance and coordination, gait disturbance
    • Mixed
    • Damage to areas listed previously
    • Symptoms from more than 1 type
    • Most common is spastic-dyskinetic CP
  46. Cerebral Palsy clinical features
    • Motor impairments
    • Communication/speech
    • -Delays in dev or difficulty speaking
    • Cognitive impairments
    • -Learning disabilities and behavioral problems
    • Visual/Hearing Problems
    • -Astigmatism and strabismus
    • Reflexes
    • Posture
    • -Head and trunk righting
    • Balance
    • -Need both hands for support
    • Oral motor function
  47. Ion Pumps
    • Formed by proteins
    • Use energy released from ATP breakdown to transport ions across membrane

    • Sodium-potassium pumps
    • Calcium pumps
  48. Diffusion
    • Get net movement of ions from area of high concentration to area of low concentration
    • Concentration gradient - ions flow DOWN gradient until EQUAL on both sides
  49. Electricity
    Difference in electrical potential across membrane as ions move
  50. Action Potential
    • Conveys info over distances in nervous system
    • Cytosol is negative; AP is a reversal of this (briefly becomes + = depolarizes)
    • Does not lessen as it moves down axon
    • Similar in size and duration for all cells
    • Convey info through frequency
  51. Properties of APs
    • Shared by axons in nervous system of ALL animals
    • Membrane potential moves from -65mV to around +40mV
  52. Parts of Action Potential
    • Rising Phase: rapid depolarization of membrane to around +40mV
    • Overshoot: when inside has (+) charge
    • Falling Phase: rapid depolarization to (-)
    • Undershoot/After-hyperpolarization: last part of falling phase when <-65mV
    • Restoration of resting potential
  53. Firing frequency of APs
    • Dependent on magnitude of depolarizing current
    • Limited; increase with increased current BUT limit to rate at which neurons fire APs (max = 1000Hz)
  54. Refractory Periods
    • Absolute Refractory Period (ARP)
    • Cannot generate another AP from ˜1 ms
    • Relative Refractory Period
    • Several seconds at end of ARP when difficult to initiate another AP
    • -Requires greater current than usual to get AP
  55. Theory of AP
    • Depolarization to threshold
    • Na+ channels open
    • Increase in permeability of Na+
    • Na+ into cell = depolarization (rising phase)
    • Close Na+ channels, open K+ channels
    • Increase permeability of K+
    • K+ out of cell = depolarization (falling phase)
  56. Voltage-gated Na+ channel
    • Selective pore to Na+
    • Opens and closes based on electrical potential of membrane
    • Na+ ion is stripped of most but not all water = whats left helps Na+ pass selectivity filter
  57. Properties of Voltage-gated Na+ Channels
    • Open with little delay
    • Stay open 1msec, then close
    • Cannot open again until Vm returns to negative value
    • Change from -80 to -65 = little effect
    • Change from -65 to -4- = open Na+ channels
    • Needs 1000s of these in a square micrometer to get an AP
  58. Channelopathy
    • Problem with Na+ Channels
    • Slowing of Na+ channel inactivation = prolonging of APs
    • -Ex. epilepsy with seizures
  59. Tetrodotoxin (TTX)
    • In puffer fish
    • Clogs Na+ pore = blocks AP
    • Paralysis of diaphragm due to nerve and muscle block
  60. Saxitoxin
    • Clams, muscles, shellfish that feed on certain dinoflagellates 
    • Blocks sodium channel
    • Fatal; paralysis of diagram due to nerve and muscle block
  61. Batrachotoxin
    • Skin on Colombian frog
    • Causes Na+ channels to open at more negative Vm and stay open longer
    • Scrambles AP code/info being sent
  62. Anesthetics
    • Bind to voltage-gated Na+ channels preventing Na+ from docking there = prevents APs
    • Affects smaller axons more then large
    • -Smaller are more dependent on all channels functioning 
    • -eliminating a few with anesthetic prevent AP in axon = no pain sensation
  63. Voltage-gated K+ channels
    • Open msec AFTER depolarization = slower to open than Na+ channels
    • Help with repolarization (falling phase)
  64. AP threshold
    Vwhere enough voltage-gated Na+ channels open so permeability of Na+ is > permeability of K+
  65. AP Rising Phase
    • Negative potential of Na+ ion
    • Driving force on Na+ ions so Na+ ions rush into cell causing rapid depolarization
    • (Na+ channels open)
  66. AP overshoot
    Na+ channels close at positive Vm BUT permeability continues to favor Na+ so Vm goes towards ENa
  67. AP falling phase
    • Na+ channels inactivate
    • K+ channels open (triggered by depolarization but take 1 msec to open)
    • -K+ rushes out of cell so Vm moves toward negative
  68. AP undershoot
    • Open voltage-gate K+ channels PLUS
    • normal membrane permeability to K = Vm toward Ek
    • Hyperpolarization UNTIL voltage-gated K+ channels close AND Na+ - K+ pump reestablishes resting potential
  69. AP absolute refractory period
    • Na+ channels are inactive once cell strongly depolarizes
    • Cannot active again (No AP can be generated) UNTIL Vm goes sufficiently negative and Na+ channels then deinactivate
  70. AP Relative Refractory Period
    Vm stays hyper polarized until Voltage-gated K+ channels even MORE current would be needed to bring Vm to threshold for AP
  71. Rules for AP Conduction
    • Goes ONE direction = does not turn back
    • Can be initiated and move EITHER direction (antidronic conduction) though usually only go one way (orthodronic conduction)
    • Velocity varies but typically 10 m/sec
  72. Factors affecting conduction
    • Na+ current during AP depolarizes patch of membrane just ahead of it
    • Speed AP goes down axon depends on how far ahead of AP the depolarization is
    • -depends on physical characteristics of axon
    • 2 paths (+) charge can take (leaky hose)
    • -Down inside of axon
    • -Across axon membrane
    • Narrow axon with many open membrane pores = slower
    • Wide axon and few open pores = faster
    • Therefore increased axon diameter = increase AP conduction velocity
  73. Factors affecting excitability
    • Axon size
    • # of voltage-gated channels
    • Smaller axons require greater depolarization to reach AP threshold (and are more sensitive to anesthetics)
  74. Saltatory conduction
    • Large axons conduct AP faster
    • Problem - take up space!
    • Solution - insulation of axon = myelin
  75. Myelin
    • Layers of glial cells (Schwann cells in PNS and Oligodendrocytes in CNS)
    • Facilitate AP movement down axon = increase conduction velocity
    • Not continuous along axon
    • Breaks where ions cross membrane to generate APs = Nodes of Ranvier
    • Voltage-gated Na+ channels are concentrated at membrane of Nodes
  76. AP conduction down an Axon
    • AP is initiated at the axon hillock
    • Electrical activity of the first AP spreads and that triggers nearby voltage-gated channels
    • Once triggered, another AP occurs in that affected spot
    • That next AP current spreads nearby and initiates another AP
  77. Saltatory Conduction
    When the AP jumps down the axon from node to node
  78. Amyotrophic Lateral Sclerosis (ALS)
    • Attacks the nerves first; demyelination begins later, after nerves have begun to die
    • "Lou Gehrig's disease"
    • Most common MND; average onset is late 50s
    • Progressive CNS degeneration
    • No cure, fatal
  79. ALS possible causes
    • Gene mutations
    • Amino acid changes
    • Excitotoxicity
    • Environmental effects
    • Neurofilament protein accumulation in cell body and axon
    • Autoimmune reaction
    • Lack of neurotrophic factors
    • -Proteins responsible for growth and survival of developing neurons and maintenance of mature neurons
  80. ALS pathology
    • Progressive degeneration of MOTOR neurons
    • Affects both upper and lower motor neurons
    • UMNs in cortex and corticospinal tracts
    • Brainstem nuclei for CNss 5,7,9,10,12
    • Anterior horn cells of CS
    • Spinocerebellar tracts and posterior column
    • NOT sensory neurons
  81. ALS symptoms
    • Early
    • Exercise intolerance
    • Weak voice
    • Decreased respiratory abilities
    • Difficulty in walking
    • Clumsiness
    • Muscle twitches
    • Progression
    • Spasticity
    • Progressive muscle weakness
    • Slurred speech = dysarthria
    • Difficulty chewing and swallowing = dysphagia
    • Upper and lower motor neuron symptoms
  82. S/S of Upper MND
    • Muscle weakness
    • Spasticity
    • Hyperreflexia
    • -Exaggerated reflexes
    • Abnormal reflex
    • -Babrinski's sign
  83. S/S of Lower MND
    • Muscle weakness
    • Atrophy
    • Fasciculations
    • Hypotonia
    • Areflexia
    • Muscle cramping
  84. Fasciculations
    • Fine movements of a small area of muscle = twitch
    • Result in minor local muscle contractions or uncontrollable twitching of single muscle group served by single motor nerve fiber or filament
  85. ALS Prognosis and Progression
    • Varies by person; no timeline
    • -10% live 10 years, 50% live 3 years
    • Eventually can't stand, walk, get out of bed, eat, do ADLs
    • Eventually can't breathe
    • Little to no cognitive changes but...memory and decisions?
  86. Multiple Sclerosis
    • Chronic, often disabling disease that attacks the CNS
    • Causes slowed or blocked transmission of signals resulting in MS symptoms
    • Randomness of location of attacks, no 2 pts present with the same symptoms
  87. Possible causes of MS
    • Inflammation = main cause of the nerve damage
    • -Antibodies that attack oligodendrocytes = demyelination
    • -Patches of demyelination called Plaques
    • Environmental factors
  88. MS possible remission/improvement
    • Re-myelination
    • Oligodendrocytes able to re-create a weaker version of the myelin sheath
    • Repeated attacks lead to fewer, less effective re-myelinations
    • Eventually hard-plaque is built up around damaged axons = "scleroses"
  89. Relapse-Remitting MS
    • Series of relapses and remissions
    • Back and forth switch between a worsening and an improving of symptoms 
    • During relapse often notice loss of function and dev. new symptoms
    • Corticosteroids often used to shorten the duration of relapses
    • Most common type
  90. Primary progressive MS
    • Slow, steady worsening of symptoms
    • Gradually become worse over time, though the rate of worsening varies greatly 
    • 10% of MS
  91. Secondary Progressive MS
    • Originally diagnosed with relapsing-remitting MS
    • -Have stopped having periods of remission and exp. a slow but steady worsening of symptoms
    • About 50% of ppl with relapsing-remitting develop this within 10 years
  92. Progressive-Relapsing MS
    • Have a steady worsening of symptoms along with exacerbations
    • Without periods of remission
    • 5% of all ppl with MS
  93. Benign MS
    • Symptom onset followed by return to normal
    • May never have another onset
    • May have ongoing incidents with return to normal
  94. Malignant MS
    • aka Marburg Variant Multiple Sclerosis
    • Particularly aggressive form; very rare
    • Swift and relentless decline to significant disability or even death
    • Often w/in a few weeks or months
  95. Multiple Sclerosis precautions
    • Patients should avoid high temperatures and excessive exercise
    • Elevated body temp interferes with activity of axon proteins resulting in decreased AP conduction
  96. MS prognosis/outcome
    • Shortens lives of women 6 years and men 11 years
    • Men more common to have progressive
    • Suicide is common
    • Most have severest disabilities within 5 years of onset
  97. Alzheimer's Disease
    • Progressive neurodegenerative disease
    • Most common form of dementia
    • Decline of intellectual abilities due to brain tissue death
    • Progresses in stages
  98. 7 stages of Alzheimer's
    • No impairment
    • Very mild cognitive decline
    • Mild cognitive decline
    • Moderate cognitive decline
    • Moderately severe cognitive decline
    • Severe cognitive decline
    • Very severe cognitive decline (late-stage Alzheimer's)
  99. Alzheimer pathology
    • Structures affected
    • Cerebral cortex decreases in size due to cell death
    • Hippocampus dramatically shrinks
    • Ventricles enlarge
    • Wernicke's area
    • Frontal lobe
    • Limbic system
    • Parietal lobe
    • Brainstem
  100. Plaques
    • Created by Beta-amyloid proteins that stick together
    • Block cell communication at synapses
    • Glial Cell Theory
    • -Amyloid Plaques = Microglial Immune Response = Inflammation/Chemical response = damage to myelin
  101. Tangles
    • Damage to cell-to-cell transport (ex. nutrients)
    • Collapses Tau protein that supports these pathways in healthy cells
    • Results in cell death and tissue loss
  102. Amyloid Plaques process
    • Beta-Amyloid build up
    • Create hard, nondisolvable plaques
    • Block synapse, dysfunctional path, cell death
  103. Neurofibrillary tangles process
    • Tau Protein Atypical
    • -Normally > in axons, now > in body and dendrites
    • Microtubules fall apart
    • -Move nutrients, removes waste, etc.
    • Create Neurofibrillary Tanges in neurons = cell death
  104. Plaque and Tangle Spreading
    • Early Alzheimers - 20+ years before diagnosis
    • Begin forming in areas of memory
    • Thinking, planning
    • Moderate Alzheimers - lasts 2 to 10 years
    • Wernicke's Area
    • Proprioception, confusion
    • Severe Alzheimers - lasts 1 to 5 years
    • Communication, recognizing people, ADL's comp
    • Cell death over majority of cerebral cortex
  105. Glial Cell theory
    • Breakdown of late-stage myelin promotes buildup of toxicamyloid-beta fibrils that deposit in brain and become plaques associated with Alzheimer's disease
    • Amyloid products destroy more and more myelin
    • Disrupt brain signaling and leading to cell death and clinical signs of Alzheimer's
  106. 10 signs of Alzheimer's
    • Memory loss
    • Difficulty with problem sovling
    • Challenges completing familiar tasks
    • Confusion with place or time
    • Vision and spatial relationship problems
    • Trouble with words in speaking or writing
    • Losing items and the ability to retrace steps
    • Impaired judgement
    • Withdrawal from social activities or work
    • Alterations in mood and personality
  107. Alzheimers prognosis
    • Irreversibly damage; no cure
    • Drug treatment can only slow progression of symptoms
    • Progresses differently for each situation
    • Final phase lasts a couple months to several years
    • -Unable to understand language
    • -Cant recognize family or friends
    • -Unable to perform ADLs
  108. Guillain-Barre Syndrome (GBS)
    • Acute Ideopathic Polyneuritis = rapid onset irritation or inflammation of many nerves of unknown cause
    • Typically occurs days to weeks after viral infection
    • Mechanism by which virus leads to GBS is not known
  109. Guillain-Barre Syndrome Pathophysiology
    • Peripheral nerves are damaged due to autoimmune response
    • Damage to myelin in peripheral nerves = decreased nerve conduction
    • Results in weakness or, if damage to axons, paralysis
    • Affects motor nerves from spinal cord to muscles (limb movements, respiration, swallowing, speech)
    • Affects sensory nerves from skin, muscles and joints to the spinal cord
    • Ascending - feet up legs to trunk to upper extremities
    • No damage to brain, spinal cord, or cranial nerves
  110. GBS sensory impairments
    • Decreased hot/cold, textures, light touch, proprioception
    • Increased parasthesias (numbness or tingling), pain
  111. GBS motor impairments
    • Decreased
    • Strength/muscle contraction
    • Coordination and balance
    • Tendon reflexes
    • ROM
    • Posture
    • Fatigue
    • Spasticity
    • Incontinence 
    • Tremors 
    • Ataxia

    Muscle atrophy
  112. Course of GBS
    • Mild: lasts days to weeks
    • -Waddling gait
    • -Tingling and weakness in extremities
    • Severe: weeks to months
    • -Paralysis
    • -Loss of breathing ability/vent dependent
    • -Loss of speech/communication

    90% of patients are at their weakest by week 3
  113. GBS phases
    • Deterioration/Acute
    • Decline, possibly to needing vent
    • Lasts up to 4 weeks
    • Poor respiratory function, joint and soft tissue pain, progressing weakness, autonomic dysfunction, fear
    • Plateau
    • Symptoms remain but don't worsen
    • Lasts days to weeks
    • Pressure areas, sensory loss, low morale, loss of movement, disorientation
    • Improvement
    • Increased movement
    • Lasts up to 2 years
    • Weakness, pain, fatigue, lack of postural sensation, tremor, autonomic dysfunction, lability, incomplete recovery
  114. Criteria to be a NT
    • Synthesized and stored in presynaptic neuron
    • Released by presynaptic neuron
    • Produces a response in postsynaptic cell
    • -Response is same when experimentally applied as that which occurs naturally upon release from presynaptic neuron
    • Locally degraded
  115. Acetylcholine (Ach)
    • NT throughout CNS and at ALL neuromuscular junctions
    • Requires enzyme = choline acetyltransferase (ChAT)
    • ChAT synthesized in soma and transported down axon
    • Only cholinergic neurons use ChAT
    • ChAT synthesizes Ach in axon terminal and Act is concentrated in vesicles
  116. Acetylcholinesterase (AChE)
    • Manufactured by Cholinergic Neurons but also by noncholinergic neurons 
    • A degrading enzyme
    • Target of nerve gases and insecticides 
    • -Disrupts transmission at cholinergic synapses on skeletal and heart muscle
    • -Decreased heart rate and BP and respiratory paralysis = death
  117. Ach Types and actions
    • Nicotine (agonist) - Curare (antagonist) - Nicotinic Receptor (receptor)
    • Muscarine (agonist) - Atropine (antagonist) - Muscarinic receptor (receptor)
  118. Tyrosine
    • Amino acid precursor for = Dopamine (DA), Norepinephrine (NE), Epinephrine (i.e. adrenaline)
    • Found in regions of nervous system that regulate mood, movement, and attention
  119. Dopamine
    • Catecholinergic Neurons
    • Tyrosine hydroxylase (TH) catalyzes 1st step in catecholamine synthesis
    • -TH converts tyrosine to dopa
    • Dopa converted to NT Dopamine by dopa decarboxylase
  120. Norepinephrine (NE)
    • Catecholinergic neurons
    • Contain TH and dopa decarboxylase AND dopaimine B-hydroxylase (DBH)
    • -This converts DA to NE
  121. Epinephrine (Adrenaline)
    • Catecholinergic neuron
    • Phentoalamine N-methyltransferase (PNMT) converts NE to epinephrine
    • Released in brain and also by adrenal gland into bloodstream
  122. Cocaine and amphetamine
    • Block catecholamine uptake = prolonged NT action in cleft
    • After uptake
    • -Loaded into vesicles for reuse
    • -Destroyed by MAO (enzyme)
  123. Serotoninergic Neurons
    • Known as 5-hydroxytryptamine (5-HT)
    • Derived from tryptophan
    • Important regulators of sleep, mood, emotions
  124. Steps to synthesize Serotoninergic neurons
    • Tryptophan converted to 5-HTP (precursor)
    • This is converted to 5-HT (Serotonin)

    • Source of brain tryptophan is blood
    • Source of blood tryptophan is diet; grains, meat, dairy
  125. Amino Acidergic Neurons
    • Amino acids
    • Glutamate (Glu)
    • Glycine (Gly)
    • Gamma-aminobutyric acid (GABA)

    • Serve as Its at most CNS synapses
    • GABA is unique to neurons that use it as NT
    • Glutamate & glycine are synthesized in ALL cells BUT glutamate is 2-3x higher in glutamatergic neurons
  126. GABA
    • Precursor is Glutamate; enzyme GAD makes GABA from glutamate
    • -GAD is widely distributed in brain
    • -Major source of synaptic inhibition in nervous system 
    • Reuptake by Na+-dependent transporters and metabolized by GABA transaminase
  127. ATP
    • Key in cellular metabolism 
    • Concentrated in many PNS and CNS synapses
    • Released in Ca2+ spikes
    • Packaged with other "classic" NTs in vesicles
  128. Endocannaabinoids
    • Small lipids released from postsynaptic neurons and act on presynaptic terminals
    • "retrograde signaling" so these are "retrograde messengers"
    • Serve as feedback system; regulate conventional synaptic transmission
    • If postsynaptic cell is inactive, tell the presynaptic cell to slow down
  129. Nitrous Oxide (NO)
    • May be retrograde messenger used to regulate blood flow
    • Very small; can diffuse quickly and to many surrounding areas
    • Break down quickly
  130. Additional functions of NTs
    • ATP - energy source for cells
    • Amino acids -  make proteins
    • NO - causes smooth muscle of blood vessels to relax
    • ACh - highest levels are in cornea where are NO Ach receptors
    • Serotonin - highest levels NOT in brain but in blood platelets
  131. Amino Acid-gated Channel
    Mediate fast synaptic transmission in CNS

    • Glutamate-gated
    • -AMPA
    • -NMDA
    • GABA-gated
    • Glycine-gated
  132. Glutamate-gated: AMPA
    • Amino Acid-gated channel
    • Permeable to Na+ and K+, NOT to Ca2+
    • Activated = allow Na+ into cell = depolarization
  133. Glutamate-gated: NMDA
    • Amino Acid-gated channel
    • Excitatory by admitting Na+
    • Permeable to Ca2+
    • Voltage-dependent = blocked by Mg+ but when stimulated moves Mg+ and Ca2+ enters and K+ moves out
  134. Glutamate as Poison
    • Cannot generate enough ATP to keep pumps working
    • -Membranes depolarize and Ca2+ leaks into cell
    • -Ca2+ entry triggers Glutamate release
    • -Further depolarizes cell so get even more intracellular Ca2+ = still more glutamate released
    • Glutamate at high levels kills neurons by overexciting them = excitotoxicity 
    • Linked to ALS and Alzheimer's
  135. GABA-gated and Glycine-gated channels
    • GABA mediates most CNS inhibition
    • Glycine mediated the rest
    • Both gate a Cl- channel
    • Too much inhibition = loss of consciousness and coma
    • Too little inhibition = seizure
  136. Benzodiazapines and Barbiturates
    • Bind to GABA channel
    • Benzo increase # of channel openings
    • Barb increased duration of channel openings
    • Both increase inhibitory Cl- current = stronger IPSPs = increase inhibition
  137. Parkinson's Disease
    • Affects nerve cells in part of brain controlling muscle movement
    • -Dopaminergic neurons in brain slowly degenerate = decreased dopa available so decreased DA
    • Progresses gradually; treatable (administer dopa; neurons keep dying so need more and more)
  138. Parkinson's deep brain stimulation
    • Electrodes placed in globus pallid us or sub thalamic nucleus
    • Connected by wires to pacemaker device in chest called an impulse generator
    • When activated, impulse generator then sends signals to inactivate the chosen area of brain that is responsible for symptoms
  139. Parkinsons Pathophysiology
    • Defect in dopamine pathway (connects the substantial nigra to the corpus striatum)
    • Involved extrapyramidal system which influences initiation, modulation, and completion of movement
    • Reduction of dopamine-creating neurons in the Substantia Nigra
    • Upsets normal balance between dopamine and ACh neurotransmitters
  140. Parkinson's causes
    • Genetic
    • Environmental
    • Medication related
  141. Parkinson's Onset
    • Earliest symptoms can be subtle
    • -An arm that doesn't swing when walking
    • -A mild tremor in the fingers of one hand
    • -Soft, mumbling speech
    • -Lack energy, depressed or have trouble sleeping
    • -Takes longer to shower, shave, eat or do other routine tasks
  142. Parkinson's Clinical signs and symptoms
    • Rhythmic tremors
    • Bradykinesia
    • -Slowed movement
    • -Slowed reaction time
    • Akinesia
    • Rigidity of muscles
    • Loss of postural reflexes
    • Decreased muscle strength and speed
    • Muscle pain
    • Delayed initiation of movements
    • Can be unilateral but progress to bilateral
    • Loss of automatic movements
    • No longer gesture or seem animated when speaking
  143. Parkinson's Gait
    • Poor balance
    • Tendency to fall backward when standing
    • Festinating gait
    • -Shuffling ambulation with small, quick, hasty steps
    • -Appears that the patient is stumbling forward as if they are "chasing" their center of gravity
    • Decreased or absent arm swing while walking
    • Decreased heel strike
    • Decreased trunk rotation
    • Decreased stride length
    • Increased stance phase
    • Cannot stop immediately and unable to turn quickly or change directions without difficulty
    • Freezing
  144. Parkinson's Prognosis
    • No cure
    • Chronic and progressive
    • Symptoms vary greatly
    • Usually symptoms worsen over an average of 15 years
    • If left untreated, can lead to deterioration of almost all brain functions, leading to death
    • If treated, life expectancy is new that of normal
    • Death may be due to respiratory issues, falls
  145. Epilepsy
    • Chronic, CNS disorder
    • Condition of recurrent, unprovoked seizures
    • 2 unprovoked seizures at least 24 hours apart
  146. Seizure
    • Sudden, abnormal electrical activity in the brain
    • Results in altered behavior, sensation, or consciousness
  147. Epilepsy pathology
    • Electrical discharges by groups of neurons in the brain that become abnormally linked
    • -While a seizure is occurring, these neurons can fire up to 500 times per second
    • -Normal firing rate is about 80 times per second
    • Permanent changes in brain tissue cause the brain to be too excitable = brain sends out abnormal signals
  148. Hyperexcitable state (epilepsy)
    Excessive excitation and/or loss of inhibition

    • Increased excitatory neurotransmitters (Glutamate)
    • Decreased inhibitory neurotransmitters (GABA)
    • Alteration in voltage gated ionic channels
    • -Channelopathy
    • --Slowing of Na+ channel inactivation
    • Intra/extracellular ionic alterations in favor of excitation
  149. Epilepsy pathology in children
    • Neuron and synapse proliferation before
    • Synapse elimination
    • Synaptic capacity
    • Synaptic rearrangement
    • Apoptosis
    • More neurons/synapses present than in adults
  150. Epilepsy symptoms
    • Temporary confusion
    • Staring spell
    • Uncontrollable jerking movements
    • Loss of consciousness and awareness
    • Seizures depend and vary on type of seizure
  151. Focal (Partial) Seizures
    • When seizures appear to result from abnormal brain activity in just one area of the brain
    • Simple: not affecting awareness (no loss of consciousness) or memory
    • Dyscognitive/complex: affect awareness or memory of events before, during and immediately after the seizure, and behavior
  152. Generalized seizures
    • Affect both cerebral hemispheres
    • Absence: staring and subtle body movement, brief loss of awareness
    • Tonic: stiffening of muscles in back, arms and legs, may fall to floor
    • Clonic: rhythmic, jerking muscle movements in neck, face and arms
    • Myoclonic: sudden brief jerks or twitches of arms and legs
    • Atonic: drop seizures; loss of muscle control causing collapsing/falls
    • Tonic-Clonic (grand mal): loss of consciousness, body stiffening and shaking, loss of bladder control
Card Set
NeuroPhys Unit 2
NeuroPhys Unit 2