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Neurobiology > Lecture 24 > Flashcards

Lecture 24 Flashcards

1
Q

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

A

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

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2
Q

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

A

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

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3
Q

two subdivisions of the mesencephalon

A

superior/inferior colliculi and the midbrain tegmentum

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4
Q

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

A

metencephalon (cerebellum and pons) and myelincephalon (medulla)

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5
Q

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

A

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

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6
Q

neurogenic decisions are made by influences from __

A

immediately neighboring cells

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7
Q

delta activation of notch leads to transcriptional repression of the __

A

bHLH neurogenic transcription factors (neurogenin)

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8
Q

delta activation of notch also represses expression of __

A

Delta itself

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9
Q

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

A

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

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10
Q

high delta expression = __ of neurogenin = __

A

expression; neuroblast

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11
Q

low delta expression = __ of neurogenin = __

A

repression; progenitor

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12
Q

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

A

inside out; youngest

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13
Q

the early neocortex contains the __

A

marginal zone

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14
Q

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

A

Cajal-Retzius (CR); Reelin; migrating

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15
Q

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

A

selective; memory and cognition; cortical

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16
Q

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

A

molecular, cellular, and physiological

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17
Q

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

A

45

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18
Q

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

A

true

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19
Q

what is the biggest risk factor for Alzheimer’s

A

age

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20
Q

other risk factors for Alz

A

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

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21
Q

why is less education a risk factor?

A

because highly educated people are more mentally active into old age

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22
Q

what is the gene for Alz and dementia

A

ApoE4

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23
Q

early symptoms

A

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

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24
Q

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

A

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)

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25
Q

how long do people usually survive after getting Alz?

A

average of 8 years

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26
Q

what is a common comorbidity that kills

A

pneumonia

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27
Q

structural changes (2)

A

ventricles get larger, cortex atrophies

28
Q

neuropathology of alz (2)

A

amyloid plaques and neurofibrillary tangles

29
Q

amyloid beta peptides are derived from the __

A

cleavage of beta-amyloid precursor proteins (APPs)

30
Q

Alz patients show numerous plaques which are composed of __

A

amyloid beta peptides

31
Q

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

A

signaling molecule at the synapse

32
Q

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

A

no

33
Q

APP is a __ protein that extends __ (__)

A

membrane; outward; signaling molecule

34
Q

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

A

beta-amyloid

35
Q

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

A

sticky; cling together; plaques seen in Alz

36
Q

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

A

synapses and dendrites

37
Q

amyloid beta disrupts __

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

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

38
Q

presenilins are crucial components of __

A

the enzymes that work to cleave APP

39
Q

mutations in presenilins cause the overproduction of __

A

insoluble forms of AB peptides

40
Q

presenilins are __ proteins

A

transmembrane

41
Q

AB levels can be elevated by __ and/or __

A

enhanced production; reduced clearance

42
Q

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

A

oligomer formation; changes of synaptic function

43
Q

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

A

oxidative stress and altered ionic homeostasis

44
Q

microtubules are like __ that __

A

railroad tracks; transport vesicles and other molecules

45
Q

tau-proteins act as railroad __ that __

A

ties; stabilize the structure of the microtubules

46
Q

in AD tau proteins become __, which __

A

tangled; unstabilizes the structure of the microtubules

47
Q

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

A

neurofibrillary tangles; hippocampus; displace normal neurons

48
Q

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

A

axonal microtubules; dendritic spine plasticity

49
Q

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

A

caspase; membrane integrity

50
Q

calcium modulates many neural processes, including __ (2)

A

synaptic transmission and cell death

51
Q

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

A

neuronal calcium regulation; intracellular calcium; death of neurons

52
Q

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

A

calcium signaling

53
Q

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

A

acetylcholine signaling; cholinergic

54
Q

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

A

striatum of the basal ganglia

55
Q

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

A

acetylcholine

56
Q

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

A

the enzyme used in the production of acetycholine

57
Q

3 types of cholinergic treatments

A

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

58
Q

additional treatments for alz

A

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

59
Q

exercise results in reduced __ and enhanced __

A

amyloid deposition; clearance of amyloid beta

60
Q

treadmill exercise has also been shown to ameliorate __

A

the accumulation of phosphorylated tau

61
Q

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

A

genetic and caused by mutations in APP or presenilin genes

62
Q

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

A

21; down syndrome

63
Q

more than half of down’s patients have __

A

early onset alz if they survive to their 30s

64
Q

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

A

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

65
Q

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

A

no specific gene mutations

66
Q

formation of AB plaques causes (2)

A

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

67
Q

decreased Ach production = less __

internalization of glutamate receptors= less __

A

synaptic activity; activity (cognitive decline)

Neurobiology (16 decks)

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