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why use macrophages and microglia in AD?
both have been shown to be associated with AB clearance in the brain
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drawbacks of IV
- to other organs
- risk microvascular entrapment
- cost
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drawbacks of surgery
- rejection of transplanted cells, inflammation
- limited repeatability
- quality of life
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what was used to determine purity of differentiated eGFP macrophages?
flow cytometry
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how are histological analysis done
eGFP macrophage treated APP/PS1 mice brain sections were stained with Iba-1 ab or monoclonal ab
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what was used to determine number of GFP cells in total cells?
qPCR
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what is one benefit for INA migration of cells?
does not dependent brain inflammation and AD pathology
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what is most common complaint in AD patients?
loss of episodic memory
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3xTgAD
homozygous for there mutant alleles APP, tau and PSEN1
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what was the shallow task and deeper task?
- shallow task: color
- deeper task: age
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physostimine
reversible cholinesterase inhibitor
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5 choice serial reaction time task
mouse initiate tril, light stimulus appear after a variable time interval, mouse must touch correct response hole to pass the trial
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between control and AD group, what was the number of omissions, latency?
same
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what was stat significant in sean's paper?
- vigilance (sustain attention for long period of time)
- difference in accuracy when stimulus shortened to 1 second or less
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response latency
after light glows, how quickly they respond to light
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magazine latency
how long it takes to respond to reward
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what did Donepezil increase?
response accuracy and vigilance
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visual impairment?
no b/c mutated mice responded as accurately during long time intervals of light
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motivation?
no b/c no difference in number of omission
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no difference in omissions?
no rats follow same pattern of attentional impaired with reduced acetylcholine levels
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free radical theory of aging
progressive imbalance between generation of reaction oxygen species and levels of antioxidant defenses
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what are the physiology of AD patients according to Kristin?
- increased lip and protein oxidative damage in lymphocyte mitochondria
- increased oxidative stress in brain
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MAPT
gene that encodes for microtubule associated protein tau
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how were the mice analyzed in Kristin's paper...the effect of voluntary physical exercise on pathology of AD?
analyzed the cerebral cortical tissue to det. soluble ab40 and ab42 and measure oxidative conditions in brain
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what are the results of voluntary exercise
- increase in LPO and GSSG levels
- reduced GPX and GR activity to control
- increased CuZn-SOD to control
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redox homeostasis
maintenance of balance of reactive oxygen species and antioxidant levels
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hormetic stress
beneficial effects of mild stress, may promote changes that induce protective gene expression.
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brain derived neurotrophic factor (BDNF)
- BDNF (affects survival and function of neurons in CNS)
- is reduced in AD patients
- high levels of BDNF produce anti-depresive effects
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sham operation
operated on mice
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BrdU
- to measure neurogenesis
- incorporated into new DNA, b/c its a thymidine analog
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how can BDNF be measured?
- by using western blot (antibodies)
- plasma BDNF measured using ELISA
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ELISA
- enzyme linked immunosorbent assay
- plate based
- detect and quantify substances using antibody, antigen interaction
- enzymes convert to color if antigen is present
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stroop test
word blue is written on red paper
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verbal fluency test
b think of all words with that
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step through avoidance task
- rats in dual compartment box
- move to second box they were shocked, experiment repeated
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why measure TrkB expression?
tyrosine kinase receptors, BDNF binds to
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how did cognitive function improve with aerobic exercise
- increase in short term memory, increase in latency time (remember being shocked)
- improves executive function in humans (word generation increase)
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what are other effects of aerobic exercise
BDNF and neurogenesis increased (BDNF control neuron survival)
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glucose measured in hyperinsulinemic euglycemic clamp
- measures insulin resistance, continuous infusion of insulin while glucose held constant to measure how sensitive tissue is to insulin
- glucose infusion=glucose uptake
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how to assess spatial learning and memory?
morris water maze test
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what factors are correlated with oxidative damage?
body weight, BPSD (behavioral psychological symptoms of dementia), ab, phosphor-tau
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what is affected with cognition
overall fitness, memory
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