Lecture 24 Flashcards
three main subdivisions of the brain and the general region they give rise to
prosencephalon (forebrain), mesencephalon (midbrain), and rhombencephalon (hindbrain)
two main subdivisions of the prosencephalon and what they give rise to
telencephalon (cerebral cortex, hippocampus, basal ganglia) and diencephalon (thalamus and hypothalamus)
two subdivisions of the mesencephalon
superior/inferior colliculi and the midbrain tegmentum
two main subdivisions of the rhombencephalon and what they give rise to
metencephalon (cerebellum and pons) and myelincephalon (medulla)
molecular regulation of neurogenesis - deciding to __ or __ is based on interactions of cell surface __ and __
proliferate or differentiate; ligands (Delta) and receptors (Notch)
neurogenic decisions are made by influences from __
immediately neighboring cells
delta activation of notch leads to transcriptional repression of the __
bHLH neurogenic transcription factors (neurogenin)
delta activation of notch also represses expression of __
Delta itself
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
high delta expression = __ of neurogenin = __
expression; neuroblast
low delta expression = __ of neurogenin = __
repression; progenitor
cortical layers are generated in a __ manner: __ neurons are on the outside
inside out; youngest
the early neocortex contains the __
marginal zone
the marginal zone contains __ cells which produce cues (__) to signal neurons to stop __
Cajal-Retzius (CR); Reelin; migrating
Alzheimer’s is associated with the __ damage of brain regions and neural circuits critical for __ ( __ dementia)
selective; memory and cognition; cortical
the pathogenesis of this disease is complex and involves many __ (3) pathologies
molecular, cellular, and physiological
only __% of alzheimer’s people report being told of their diagnosis
45
alzheimer’s is the most common cause of dementia in adults. true/false
true
what is the biggest risk factor for Alzheimer’s
age
other risk factors for Alz
family history of alz or dementia, lots of exposure to neurotoxins, history of TBI, less educated, viral infection (CID)
why is less education a risk factor?
because highly educated people are more mentally active into old age
what is the gene for Alz and dementia
ApoE4
early symptoms
short term memory deficits, problems with navigation, word finding difficulty, organization/problem solving, withdrawal, clearly worsening over time
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)
how long do people usually survive after getting Alz?
average of 8 years
what is a common comorbidity that kills
pneumonia
structural changes (2)
ventricles get larger, cortex atrophies
neuropathology of alz (2)
amyloid plaques and neurofibrillary tangles
amyloid beta peptides are derived from the __
cleavage of beta-amyloid precursor proteins (APPs)
Alz patients show numerous plaques which are composed of __
amyloid beta peptides
APPs normal function in the brain is unclear but it may be a __
signaling molecule at the synapse
is beta-amyloid build-up necessarily predictive of Alz?
no
APP is a __ protein that extends __ (__)
membrane; outward; signaling molecule
enzymes cut APP into fragments, the most significant fragment type for alz is __
beta-amyloid
insoluble beta-amyloid peptides are __ so fragments __ along with other molecules outside of the cell, forming the __
sticky; cling together; plaques seen in Alz
soluble beta-amyloid peptides also damage __ in addition to forming plaques
synapses and dendrites
amyloid beta disrupts __
- soluble AB binds to __
- bindings leads to internalization of __
- __ internalization leads to decreased activity in __
synaptic transmission; synaptic sites; AMPA and NMDA receptors; glutamate receptors; synapses
presenilins are crucial components of __
the enzymes that work to cleave APP
mutations in presenilins cause the overproduction of __
insoluble forms of AB peptides
presenilins are __ proteins
transmembrane
AB levels can be elevated by __ and/or __
enhanced production; reduced clearance
the relative increase of AB42 enhances __, which causes subtle and then increasingly severe and permanent __
oligomer formation; changes of synaptic function
over time, these events result in __ (2) and a host of additional biochemical changes
oxidative stress and altered ionic homeostasis
microtubules are like __ that __
railroad tracks; transport vesicles and other molecules
tau-proteins act as railroad __ that __
ties; stabilize the structure of the microtubules
in AD tau proteins become __, which __
tangled; unstabilizes the structure of the microtubules
abnormally phosphorylated tay proteins result in __ especially in the __ or in brain structures connected to it, which __
neurofibrillary tangles; hippocampus; displace normal neurons
tau is normally largely bound to __ and plays a role in __
axonal microtubules; dendritic spine plasticity
accumulation of tau in the soma is associated with __ activation and disruptions of __
caspase; membrane integrity
calcium modulates many neural processes, including __ (2)
synaptic transmission and cell death
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
every gene that is known to increase risk of alz also modulates some aspect of __
calcium signaling
decrease in synaptic transmission is also due to a reduction in __ (__ hypothesis)
acetylcholine signaling; cholinergic
the basal forebrain is a collection of structures located ventral to the __
striatum of the basal ganglia
the basal forebrain is the major source of __ which is widely distributed in the brain
acetylcholine
at the biochemical level, alz is characterized by a reduction in __
the enzyme used in the production of acetycholine
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
additional treatments for alz
antioxidants, anti-inflammatories, anti-depressants; estrogen (does not help women); immunotherapy trials; beta secretase inhibitor
exercise results in reduced __ and enhanced __
amyloid deposition; clearance of amyloid beta
treadmill exercise has also been shown to ameliorate __
the accumulation of phosphorylated tau
most cases of early onset (30s 40s) alz are __
genetic and caused by mutations in APP or presenilin genes
genes mutated are associated with chromosome __ (same as __)
21; down syndrome
more than half of down’s patients have __
early onset alz if they survive to their 30s
the various mutations cause people to secrete a higher fraction of the __
insoluble AB peptides (mutated AB fragments and/or over production)
in late onset alz (65+), there are __ that are associated with the inheritance of the disease
no specific gene mutations
formation of AB plaques causes (2)
inflammatory response that kills neurons, and destabilizes Ca regulation leading to excitotoxicity (cortical atrophy)
decreased Ach production = less __
internalization of glutamate receptors= less __
synaptic activity; activity (cognitive decline)
