Lecture 24 Flashcards Preview

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Flashcards in Lecture 24 Deck (67):
1

three main subdivisions of the brain and the general region they give rise to

prosencephalon (forebrain), mesencephalon (midbrain), and rhombencephalon (hindbrain)

2

two main subdivisions of the prosencephalon and what they give rise to

telencephalon (cerebral cortex, hippocampus, basal ganglia) and diencephalon (thalamus and hypothalamus)

3

two subdivisions of the mesencephalon

superior/inferior colliculi and the midbrain tegmentum

4

two main subdivisions of the rhombencephalon and what they give rise to

metencephalon (cerebellum and pons) and myelincephalon (medulla)

5

molecular regulation of neurogenesis - deciding to __ or __ is based on interactions of cell surface __ and __

proliferate or differentiate; ligands (Delta) and receptors (Notch)

6

neurogenic decisions are made by influences from __

immediately neighboring cells

7

delta activation of notch leads to transcriptional repression of the __

bHLH neurogenic transcription factors (neurogenin)

8

delta activation of notch also represses expression of __

Delta itself

9

interactions of delta and notch create an imbalance where in some cells __ and in others __

delta is high and notch is low; delta is low and notch is high

10

high delta expression = __ of neurogenin = __

expression; neuroblast

11

low delta expression = __ of neurogenin = __

repression; progenitor

12

cortical layers are generated in a __ manner: __ neurons are on the outside

inside out; youngest

13

the early neocortex contains the __

marginal zone

14

the marginal zone contains __ cells which produce cues (__) to signal neurons to stop __

Cajal-Retzius (CR); Reelin; migrating

15

Alzheimer's is associated with the __ damage of brain regions and neural circuits critical for __ ( __ dementia)

selective; memory and cognition; cortical

16

the pathogenesis of this disease is complex and involves many __ (3) pathologies

molecular, cellular, and physiological

17

only __% of alzheimer's people report being told of their diagnosis

45

18

alzheimer's is the most common cause of dementia in adults. true/false

true

19

what is the biggest risk factor for Alzheimer's

age

20

other risk factors for Alz

family history of alz or dementia, lots of exposure to neurotoxins, history of TBI, less educated, viral infection (CID)

21

why is less education a risk factor?

because highly educated people are more mentally active into old age

22

what is the gene for Alz and dementia

ApoE4

23

early symptoms

short term memory deficits, problems with navigation, word finding difficulty, organization/problem solving, withdrawal, clearly worsening over time

24

diagnostic criteria for dementia = __ impairment severe enough to cause __ or __ disability in __ and one other domain such as __

cognitive; social or occupation; memory; aphasia (language disturbance), apraxia (impaired motor activities despite intact motor function), agnosia (failure to recognize or identify objects despite intact sensory function), disturbance in executive function (planning, sequencing, organization, etc), or disturbance of visuospatial skills (manifested by environmental disorientation and difficulty copying figures)

25

how long do people usually survive after getting Alz?

average of 8 years

26

what is a common comorbidity that kills

pneumonia

27

structural changes (2)

ventricles get larger, cortex atrophies

28

neuropathology of alz (2)

amyloid plaques and neurofibrillary tangles

29

amyloid beta peptides are derived from the __

cleavage of beta-amyloid precursor proteins (APPs)

30

Alz patients show numerous plaques which are composed of __

amyloid beta peptides

31

APPs normal function in the brain is unclear but it may be a __

signaling molecule at the synapse

32

is beta-amyloid build-up necessarily predictive of Alz?

no

33

APP is a __ protein that extends __ (__)

membrane; outward; signaling molecule

34

enzymes cut APP into fragments, the most significant fragment type for alz is __

beta-amyloid

35

insoluble beta-amyloid peptides are __ so fragments __ along with other molecules outside of the cell, forming the __

sticky; cling together; plaques seen in Alz

36

soluble beta-amyloid peptides also damage __ in addition to forming plaques

synapses and dendrites

37

amyloid beta disrupts __
1. soluble AB binds to __
2. bindings leads to internalization of __
3. __ internalization leads to decreased activity in __

synaptic transmission; synaptic sites; AMPA and NMDA receptors; glutamate receptors; synapses

38

presenilins are crucial components of __

the enzymes that work to cleave APP

39

mutations in presenilins cause the overproduction of __

insoluble forms of AB peptides

40

presenilins are __ proteins

transmembrane

41

AB levels can be elevated by __ and/or __

enhanced production; reduced clearance

42

the relative increase of AB42 enhances __, which causes subtle and then increasingly severe and permanent __

oligomer formation; changes of synaptic function

43

over time, these events result in __ (2) and a host of additional biochemical changes

oxidative stress and altered ionic homeostasis

44

microtubules are like __ that __

railroad tracks; transport vesicles and other molecules

45

tau-proteins act as railroad __ that __

ties; stabilize the structure of the microtubules

46

in AD tau proteins become __, which __

tangled; unstabilizes the structure of the microtubules

47

abnormally phosphorylated tay proteins result in __ especially in the __ or in brain structures connected to it, which __

neurofibrillary tangles; hippocampus; displace normal neurons

48

tau is normally largely bound to __ and plays a role in __

axonal microtubules; dendritic spine plasticity

49

accumulation of tau in the soma is associated with __ activation and disruptions of __

caspase; membrane integrity

50

calcium modulates many neural processes, including __ (2)

synaptic transmission and cell death

51

Mutant AB peptide has been shown to destabilize __, leading to an increase in __ which can trigger the __

neuronal calcium regulation; intracellular calcium; death of neurons

52

every gene that is known to increase risk of alz also modulates some aspect of __

calcium signaling

53

decrease in synaptic transmission is also due to a reduction in __ (__ hypothesis)

acetylcholine signaling; cholinergic

54

the basal forebrain is a collection of structures located ventral to the __

striatum of the basal ganglia

55

the basal forebrain is the major source of __ which is widely distributed in the brain

acetylcholine

56

at the biochemical level, alz is characterized by a reduction in __

the enzyme used in the production of acetycholine

57

3 types of cholinergic treatments

cholinomimetic (drugs that mimic the action of acetylcholine, do improve mnemonic function to a limited extent), acetylcholnesterase inhibitors, and glutamate (NMDA) antagonist memantine

58

additional treatments for alz

antioxidants, anti-inflammatories, anti-depressants; estrogen (does not help women); immunotherapy trials; beta secretase inhibitor

59

exercise results in reduced __ and enhanced __

amyloid deposition; clearance of amyloid beta

60

treadmill exercise has also been shown to ameliorate __

the accumulation of phosphorylated tau

61

most cases of early onset (30s 40s) alz are __

genetic and caused by mutations in APP or presenilin genes

62

genes mutated are associated with chromosome __ (same as __)

21; down syndrome

63

more than half of down's patients have __

early onset alz if they survive to their 30s

64

the various mutations cause people to secrete a higher fraction of the __

insoluble AB peptides (mutated AB fragments and/or over production)

65

in late onset alz (65+), there are __ that are associated with the inheritance of the disease

no specific gene mutations

66

formation of AB plaques causes (2)

inflammatory response that kills neurons, and destabilizes Ca regulation leading to excitotoxicity (cortical atrophy)

67

decreased Ach production = less __
internalization of glutamate receptors= less __

synaptic activity; activity (cognitive decline)