Lectures 11+12 Flashcards
axon degenerates when separated from cell body
Wallerian degeneration
changes in cell body
chromatolysis
How can peripheral neurons grow back after degeneration?
nerve “stump” or tract persists after axon degenerates –> peripheral axons grow back through this stump
Regenration is due to the ____. Occurs easily in __ but not the ___.
environment
PNS
CNS
Why is the environment in the PNS is hospitable to regeneration?
- machrophages rapidly remove myelin debris
- Schwann cells promote axon regeneration
- axon growth-promoting signals
Why doesn’t regeneration occur in the CNS?
- components of myelin inhibit axon growth
- absence of growth-promoting substances
- astrocytes proliferate at site of injury and form glial scar tissue that blocks axon growth
- neuron itself has decreased ability to enter “growth state”
Cognitive decline with age varies among ___ and among ___.
individuals
tasks
What causes brain shrinkage with age?
decreased number of spines and therefore synapses (not decreased neurons!) –> synaptic de-differentiation?
___ in monkeys has shown to protect to an extent from age-related cognitive decline.
exercise and caloric restriction
progressive loss of structure and/or function of neurons
neurodegeneration
Neurodegeneration most commonly affects what?
movement and/or mental function
What are some characteristics of neurodegeneration?
- incurable
- many caused by genetic mutations
- loss of neurons and synapses
- accumulation of toxic intra- or extracellular proteins
a form of dementia (i.e., loss of brain function) that gradually gets worse over time and is caused by progressive neurodegeneration
Alzheimer’s
Alzheimer’s affects ___, ___, and ___. Early onset is often ___ and late onset is more common. Symptoms first appear as “____”
memory thinking behavior genetic common forgetfulness
hyperphosphorylated tau (microtubule- associated protein) found in Alzheimer’s neurons
tangles
clumps of beta-amyloid protein found outside of neurons in patients with Alzheimer’s
plaques
Amyloid deposition leads to what?
impaired learning and memory
Infusion of beta-amyloid into lateral ventricles leads to what?
impaired spatial memory
Where are beta-amyloid seen mostly?
in the hippocampus and regions of neurogenesis
In Alzheimer’s, there is a decrease in both ___ and ___ of neurons in the dentate gyrus. Neurogenesis is also inhibited in the ___.
SVZ
Studies have shown that in the first week after a stroke (ischemia), there is increased ____ of stem cell, even in areas outside of the ___.
proliferation
SVZ/SGZ
____ increase neurogenesis in adults. __ and ___ inhibit neurogenesis.
antidepressants
stress
depression
What are the current sources of neural stem cells?
embryonic - isolated from a blastocyst
somatic cells - induced pluripotent stem cells (skin cell)
adult - isolated from stem cell niches
What are some cell replacement strategies?
mobilizing endogenous NSC (antidepressants)
transplantation
layer of cells that surrounds blastocyst
trophoblast
hollow cavity inside blastocyst
blastocoel
~30 cells at one end of the blastocoel (stem cells)
inner cell mass
What are “embryo-safe” stem cells?
single-cell biopsy from blastomere (8- cell stage) 80% survival rate (consistent with non-biopsied embryos)
What are iPSCs?
induced pluripotent stem cells; “de-differentiate” cells whose developmental fates had been previously assumed to be determined
How do you de-deifferentiate a somatic cell?
genetically reprogram adult cells to an embryonic stem cell–like state by forced expression of stem cell-specific genes and factors
What are the “4 magic genes” that need to be force expressed for de-differentiation?
Sox2: self-renewal Oct4: differentiation switch Klf4: p53 pathway, oncogene c-Myc: global histone acetylation, oncogene
What are some issues with ESCs?
- ethical issues
- difficult to access
- immunologic rejection if transplanted
What are some issues with iPSCs?
- low efficiency
* virus + oncogenes
What are some issues with adult stem cells?
- not easily accessible
- critical for normal neurological function
- immunologic rejection if transplanted
What is a potential source of autologous NSCs for transplantation?
filum terminale
What are the advantages of the filum terminale?
- expendable
* easily accessible
What is the filum terminale?
vestigial remnant of spinal cord (i.e., no critical CNS function in adults)
Why is selective or global degeneration (such as ALS or stroke) harder to treat with stem cells?
harder to establish the specific afferent-efferent and/or long-distance/local connections; more complicated than just replacing cells
What are some issues with stem cells?
- environmental cues: gliogenic cues overcome neurogenic cues
- production of ectopic circuits
- tumor formation
Where are oxytocin and vasopressin hormones produced?
magnocellular cells of the hypothalamus
What are the roles of oxytocin?
- acts on uterus during childbirth
- acts on mammary glands during lactation
- promotes mother-infant bonding
What are the roles of vasopressin?
- acts on kidney to control salt balance and blood volume
* promotes social memory (previously encountered individuals)
What happens when you inject a vasopressin antagonist in male prairie voles?
blocks pair bond formation (more like meadow voles)
What happens when you inject an oxytocin antagonist in female prairie voles?
block pair bond formation (more like meadow voles)
What happens when you express more vasopressin receptors in meadow voles?
enhance pair bond formation (more like prairie voles)
What have studies shown about men with allele 334 of vasopressin receptor (“cheating gene”)?
• felt weaker bond with partner
• more likely to have had marital crisis
in past year
• wives were less satisfied with relationship
What affect does oxytocin nasal spray have on humans?
unfamiliar faces perceived to be more trustworthy and more attractive by both males and females
When is oxytocin released?
- pair bonding and sex
- mother-infant bonding
- birth
- lactation
Children who experience neglect have long-lasting problems with ___
as well as lower ___ levels. In rats, higher levels of ____ lead to higher levels of oxytocin receptors in offspring, this persists into adulthood. Aka, early experience can have ___.
social bonding
vasopressin and oxytocin
maternal care
long-lasting effects
disorder of social behavior; lack of social engagement; poor performance on tests like perceiving emotions on faces
autism
What are some characteristics of autism?
- inability to form emotional bonds with others (including parents)
- impairment in communication skills, including spoken language
- repetitive and stereotyped behaviors
In one experiment, men with autism were less likely to recognize emotion and ___ improved this ability. It also boosted brain activity in ___. However, other studies have shown that ____ is not uniquely associated with disease.
oxytocin
amygdala and PFC
oxytocin
distortion of thinking and perception
schizophrenia
What are some symptoms of schizophrenia?
- disorganized thoughts – “loose associations”
- disorganized language – word salad, echolalia
- delusions of influence, grandeur, or persecution
- hallucinations
- bizarre behavior
- inappropriate or flat affect
- lack of motivation
- lack of insight
What are the characteristics of schizophrenia?
- late onset (teens, early 20s)
* psychotic episodes with “positive” symptoms alternate with periods of “negative symptoms” –> lifelong
What is the dopamine hypothesis of schizophrenia?
- hyperactivity of dopaminergic transmission responsible for schizophrenia
- block D2 receptors - antipsychotic drugs
- doesn’t explain negative symptoms
What were the treatments for schizophrenia?
1) psychotherapy
2) electroshock
3) lobotomy
4) antipsychotic drugs
What are the genetic influences for schizophrenia?
• high concordance (~50%) in
monozygotic twins
• 20% concordance in dizygotic twins (no more similar than other siblings)
How do antipsychotic drugs work?
block dopamine receptors
response to threat, absence of people/objects
that signify safety
anxiety
Balance in favor of GABA (high) leads to what symptoms?
sedation, amnesia, ataxia
Attenuation of GABA (low) leads to what?
arousal, anxiety, restlessness, insomnia
What is used to treat anxiety disorders?
GABA agonists - increase inhibition
recurrent and persistent thoughts, impulses, or images that are intrusive/unwanted and caused marked anxiety and distress
obsessions
behaviors people perform to reduce/remove anxiety caused by obsessions
compulsions
pervasive pattern of preoccupation with orderliness and perfectionism at the expense of flexibility and efficiency
OCD
What are the characteristics of OCD?
- preoccupation with details, rules, and lists so that the point of the activity is lost
- perfectionism that interferes with task completion
What is the serotonin hypothesis?
antidepressants that block serotonin uptake also have anti-obsessional activity –> low serotonin leads to OCD
What is PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus)?
psychiatric symptoms such as OCD and tics (uncontrolled movements) in children causes by molecular mimicry from strep
What affected areas seem to contribute to OCD?
orbitofrontal cortex, basal ganglia, striatum
What happens during molecular mimicry?
cross reactivity of antibodies
produced against a group A streptococcal carbohydrate epitope, also recognize an antigen on the surface of neurons –> immune system recognizes self antigens as foreign
How does PANDAS cause tics?
1) antibodies produced against surface protein of dopaminergic neurons –> cannot modulate dopamine release –> too much dopamine
2) antibodies produced against D2 receptor –> binding of antibodies causes a reduction of inhibitory effect
- -> more dopamine is released
**promote movement (e.g., tics)
What can be used to treat PANDAS?
• cognitive behavioral therapy and/or anti-obsessive medications (e.g., SSRI)
• antibiotics to eliminate strep infection
• “blocking” antibodies to complex with antibodies
produced by your body
• prophylactic treatment to prevent future infections
