Midterm outline Flashcards
(161 cards)
1
Q
midbrain primary morphogen
A
Wnt/BMP
2
Q
Alar plate
A
sensory region of gray matter = dorsal
3
Q
Basal plate
A
motor region of gray matter = ventral
4
Q
astrocytes
A
fibroblasts of the brain
5
Q
microglia
A
macrophages of the brain
resident immune cells of the brain
6
Q
genomic methylation
A
remyelination req DNA methylation
7
Q
Non-genomic methylation
A
myelin sheath req Protein and Lipid methylation
8
Q
Glycogen synthase
A
catalyzes formation of primary structure
- Polymerizes alpha1,4
- Transfers glucosyl from UDP glucose
ACTIVATED WHEN DEPHOSPHORYLATED
9
Q
Glycogen phosphorylase
A
cleaves alpha1,4 linked glucose until 4 residues form alpha 1,6 linkage
ACTIVATED WHEN PHOSPHORYLATED
10
Q
Debranching enzyme (“AGL”)
A
has two actions
- glucosyl transferase
- alpha1,6 glucosidase activity, releasing glucose from branch point
11
Q
ionotropic
A
direct
rapid postysynaptic responses
receptor is an ion channel
12
Q
metabotropic
A
indirect
13
Q
botulism
A
toxin produced by clostridium bacteria
taken up by motor neurons –> causes muscle wekaness/paralysis by impairing NT release at NMJ
14
Q
tetanus
A
toxin produced by clostridium bacteria
caused by wound infection by clostridium spores
taken up by interneurons that usually offer inhibitory infomration to spinal cord
therefore, release inhibition –> hyperexcitability, esp of extensors; tetanic contractions
loss of synaptic inhibiton on spinal motor neurons
15
Q
alpa latrotoxin
A
black widow spider
calcium independent NT release –> freq end plate potentials, muscle spasm, cramping, pain
16
Q
nernst potential for sodium
A
60
17
Q
nernst potential for calcium
A
125
18
Q
nernst potential for potassium
A
-90
19
Q
nernst potential for cl
A
-80
20
Q
long term potentiaition
A
brief, high freq stimulus train
400 Hz 25 ms
21
Q
long term depression
A
long (10-15min) low freq (1hz) stimuli
22
Q
“coincidence detector”
A
NMDA can detect when two are firing at once; those that fire together wire together
Mg needs a certain threshold to dissociate, so know if two axons are firing
23
Q
Glutamate
A
- major excitatory transmitter
- Calcium dep exocytosis
- synthesized by glia
24
Q
holoprosencephaly
A
incomplete cleavage of prosencephalon
lateral ventricles fuse
25
signaling centers
generate **positional** informaion; ANR, ZLI, IsO
26
hox genes
responsible for hindbrain segmentation
convey positional value along AP axis
recall: hindbrain developmental units are the rhombomeres
27
symmetrical cell division timeline
day 0-42
28
asymmetric cell division timeline
starts at day 42
29
neurogenesis
progenitor pool expansion and asymmetric cell division
30
whats going on in the ventricular zone
cells are actively dividing
31
cause of microcephaly
head circumference significantly smaller
due to imbalance between proliferation and differentiation
32
neuronal migration disorders
lissencephaly
agyria
polymicrogyra
neuronal heterotropia
33
double cortex syndrome
band of neurons stuck in white matter
34
paired pulse short term facilitation
residual calcium increases the probability of NT release (presynaptic event)
35
paired pulse short term depression
deplete the NT stores with successive stimuli; presynaptic event
36
long term potentiation mechanism
* brief, high frequency stimulus = stimulus train = tetanus
* causes depol that opens NMDA channel, calcium rushes in and then causes more AMPA channels to be inserted on the membrane --\> next time, stornger resposne to same stimulus
37
long term depression mechanism
* long, low freq stimulus
* depolarization opens NMDA channel and calcium rushes in but due to the length of low freq stimulus, the timing of the calcium activates a dif pathway
* results in AMPA channels being removed from post-synaptic membrane
* next time, weaker response
38
normal synaptic transmission
single AP in one or two axons, small EPSP and no LTP; **irrelevant stimuli are not remembered**
39
cooperativity
strong, coordinated activity (strong input) gives suprathreshold EPSP and LTP; allows for **important stimuli to be remembered**
40
associativity
stimulation of strong and weak inputs together cause LTP in both pathways; weak stimuli become significant when paired with strong stimulus --\> ASSOCIATIVE LEARNING
41
synapse specificity
**unstimulated** synapse DOES NOT undergo LTP evne if strong stimulation of neighboring synapses
means **memories** are **formed SELECTIVELY at active synapses**
42
enzyme that makes dopamine
tyrosine hydroxylase
43
enzyme that makes acetylcholine
choline acetyltransferase
44
enzymes that makes serotonin
tryptophan hydroxylase
45
PCPA
drug that competes with trp and binds irreversibly to TPH (tryptophan hydroxylase)
## Footnote
**blocks 5HT synthesis**
46
what kind of gating is the NMDA channel
ligand gated
but the magnesium is voltage gated
47
netrin DCC
attraction; for axonal guidance
axons are responsibe only before crossing
48
Slit roundabout (ROBO)
repulsive q
responsibeness is down regulated at the midline, upregulated after crossing
49
embryonic period
week 0-8 of gestation
50
what do the neural crest cells create?
peripheral nervous system!
51
what are different types of neural tube closure defects?
anencephaly =upper portion
spina bifida = lower portion
52
what are the three primay brain vesicles
1. prosencephalon
2. mesencephalon
3. rhombencephalon
53
what comes from the prosencephalon
telencephalon and diencephalon
54
what comes from telencephalon
cerebrum
55
cortical plate
dense, area which is the future cerebral cortex
56
what causes microcephaly
imbalance between proliferation and differentiation causing a depeted progenitor pool and therefore a small brain (can be due to genetic causes or environmental factors)
57
double cortex syndrome
band of neurons stuck in white matter
58
when does cerebellum develop
wk7
59
when does thalamus develop
wk8-9.5
60
what is the function of arachnoid villi?
**reabsorb** the CSF
if not working--\> can cause **hydrocephaly**
61
what is the funciton of the choroid plexus?
secrete CSF
if not working correctly --\> can cause hydrocephaly
62
sulcans limitans
divides alar (dorsal) and basal (ventral) plate cells
63
spina bifida occulta
occurs because the caudal portion of the neural tube does not close properly; therefore there is a **bony defect** often with a tuft of hair or skin dimple
there is **no herniation** of either the meninges or the neural tissue
64
meningocele
subtype of spina bifida, which occurs due to the caudal poriton of the neural tube not closing appropriately
the **meninges** **herniates** through the **bony defect,** but the neural tissue remains in place
65
meningomyelocele
subtype of spina bifida, which occurs because the caudal portion of the neural tube does not close properly
**both neural tissue and meninges herniate** through the **bony defect**
66
charcot marie tooth
* motor and sensory neuropathy, muscle weakness
* either defect in protein for myelination or protein for axon transport (mitofusion)
67
mitofusin
* controls mitochondrial transport and fusion
* mutated in charcot marie tooth
68
NMNAT2
axon survival factors; need to get all the way to the distal axon, otherwise, trigger self destruction
69
absolute risk
chance of developing the disease
70
relative risk
% elevation in risk if risk behavior continues
% reduction in risk if risk behavior stops
RR = incidence in exposed/incidence in unexposed
71
attributable risk
excess chance of disease if an exposure continues
72
attributable risk fraction
proportion of cases of disease due to an exposure or behavior
73
confidence interval
two numbers calculated from sample statistics that determine a range which is likely to include true pop parameter
74
standard error
variablility of many sample means
SE = SD/sqrt n
75
a standard error is always ....
SMALLER than standard deviaiton
76
what happens as confidence level increases
interval widens
77
what happens as the standard error increases
interval widens
78
what happens as the sample size increases
interval narrows
79
Proportions and variance
variance = pq
q = 1-p
stdev = sqrt pq
80
estimation
type of statistical inferenec where the statistic estimates a parameter
**s**tatistic=**s**ample, **p**arameter=**p**opulation
81
what does AMPA gate
sodium
82
what does NMDA gate
calcium entry
83
nicotinic ACh receptor gates
Na and K
84
muscarinic ACh receptor gates
opens K and closes Ca channels
85
Lambert-Eaton syndrome
autoimmune disease; pt makes antibodies to Ca channels
reduced presynaptic release of Ach
tx: drug prevents acetylcholinesterase
86
asymmetric
excitatory
have **thick post-synaptic density**
87
symmetric
inhibitory
have equal density on either side
88
natural opiates
endorphin neuropeptides
decrease Ca influx
decr NT release
do this by releasing **serotonin** or **NE** --\> activates opioid interneurons and suppresses spinothalamic tract neurons
may incr K conductnace
opiates decrease the amplitutde of the postsynaptic potential
89
what does the myelencephalon give?
medulla oblongata
90
what does the metencephalon give?
pons and cerebellum
91
in humans when is cortical neurogenesis completed by?
week 16 (day 108)
92
what environmental agents can cause microcephaly?
ZIKA virus (or other viral agents) and maternal alcohol consumption (fetal alcohol syndrome )
93
when do gyrations get added to the brain
at the end of pregnancy around 9 mo
94
organizing center
helps develops boundaries (like isthmic organizer --\> between midbrain and hindbrain)
HOX genes end in rhombomere 1 which develops into cerebellum
hindbrain has 8 rhombomeres (variably express hox gene and the expression overlaps)
95
Fgf8
secreted by ishthmic organizer the boundary between midbrain and hindbrain
96
retinoids
play **regulatory role** in hox gene expression (induce differential hox gene expression)
vitamin a derivative (vit a deficiency in pregnancy or ingestion of high vit a can cause brain malformation)
considered a **morphogen**
(pattern of hox gene expression overlaps)
97
B1deficiency
**pyruvate dehydrogenase**
Beri Beri = peripheral neuropathy with parethesis, numbness, pain
Wernike Korsakorff
98
alar plate would be located in which part of midbrain
the superior and inferior colliculi
99
basal plate would be located in which part of the midbrain
ventrally, motor nuclei; efferents
but dorsal to the SN and CC
100
location of sensory v motor in pons
sensory (alar plate) located on side
motor (basal plate) located in the middle
101
what is a key finding with B12 deficiency
spinal cord myelin degeneration
102
niacin b3 deficiency
this is the ONLY vitamin we can synthesize!!!
serotonin synthesis is impaired due to deficiency in dietary tryptophan
103
folic acid deficiency
B9 deficiency
neural tube defect
defective purine and pyrimiding biosynthesis
\*\*\*impacts the conversion of homocystine to methionine (which is also something that B12 does)
104
Product of SAM methylations
is SAH (S-adenosyl homocysteine) which is cleaved to homocysteine
105
Uses of SAM
**creatine synthesis –** major
Norepinephrine --\> **epinephrine**
nucleotides --\> methylated nucleotides
phosphatidylethanolamine --\> phosphatidylcholine; acetylserotonin --\> **melatonin**
106
where does SAM come from
it is a metabolite of methionine
107
causes of B12 deficiency
either lack in diet (comes from ANIMAL PRODUCTS because its synthesized by bacteria)
OR
issue with uptake (lack intrinsic factor --\> old age, surgery)
108
common neuro symptoms of B12 deficiency
**diminished vibration sensation with proprioception in legs**
weakness
depression
cognitive impairment
109
what induces basal plate
SHH
110
risk
probability of disease occuring during a **defined time period** within a defined population that is FREE OF DISEASE
111
risk factor
either part of causal chain or exposes indv to causal chain
112
what kind of study is an odds ratio used in
case control
113
point estimate
a single sample statistic used as an estimate
114
reduced ankle jerk
sign of b12 deficiency
115
Lhermittes sign
flexing neck results in electrical shock like sensation
sign of B12 deficiency
116
how much of glycogenolysis is accomplished by glycogen phosphorylase?
30% then AGL comes in and then afterwards the rest of it can be broken down
117
what are some proteins associated with glycogen
phosphorylase --\> important because allows activation of glycogen synthase
important b/c without maylin, may get extra proteins hanging out there which can affect the solubility
AMPK is another one associated --\> promotes energy generation and inhibits energy consumption; appetitie stimulation
118
AMPK
assoc with glycogen
promotes energy generation and inhibits energy consumption; appetitie stimulation
**inhibits ACC (acetylcoA--\>malonyl CoA)**
**(ACC=acetylcoa carboxylase)**
119
g6P ase
astrocytes dont have it so they cant remove the phosphate and cant release glucose; therefore they make lactate
120
what is the product of glycogenolysis in the neuron and astrocytes
lactate
121
glial fibrillary acidic protein
astrocytes (a type of glial cells) start to release this which is an intermediate
122
myelin basic protein
MBP needs to be
123
gap region has
progenitor cells
- neural progenitors
- glial progenitors
124
dense core vesicle
neuropeptide
some NT
125
what two enzymes is B12 a cofactor for
methionine synthase
methyl malonyl-co A mutase
126
where is homocysteine converted to methionine
cytoplasm
B12 is a cofactor
methycobalamin is the helper
127
where is methylmalonyl co A converted to succinyl Co A
mitochondria
adenosylcobalamin is the helper
succinylco a can then enter TCA cycle
128
what kind of methylation is MBP
arginine methylated
129
how did they induce demyelination in the mice
lysolecithin
130
what systemic result can you see in elevated homocysteine
incr inflammation and pro-inflam cytokines
131
what does elevated MMA do to myelination
inhibit it
132
what fatty acid results do you see in a methyl malonylco A mutase deficiency
aka B12 deficiency, b/c b12 is a cofactor for methyl malonyl co A mutase, which converts methyl malonyl co A to succinyl co A for the TCA cycle
you will get a buildup of branched chain FA
incr propionyl co a will cause formation of odd chain fa
133
where is the majojrity of the glycogen in the brain
astrocytes; levels 100x less than in muscle and hepatocytes
134
TGF beta pathway
type I and type II receptor (type II is dominant negative)
Transcription factor (Smad)
gene activation
135
necrosis
messy, debris, inflammation
provoked
not self initiated
136
neurotorphins
essential for development
incldue NGF, BDNF
activate tyrosine receptor kinase receptors
137
cleaved forms of neurotrophins
promote survival
| (specific for TrkA, TrkB, TrkC)
138
pro forms of neurotrophins
activate p75NTR --\> TRIGGERS CELL DEATH
139
where do oligodenddrocyte precursor cells come from
subventricular zone
140
what signals modulate myelin biogenesis
PTEN!!! which modulates Akt/mTOR
141
AKT
promotes survival
142
myelin distribution during oligodendrocyte differentiation
starts out symmetrical but becomes increasingly asymmetrical as the OLG is contact forming and then myelinating
143
what do ECM factors do to oligodendrocytes
**laminin** and **fibronectin** bind to receptors on oligodendrocytes
the receptors = integrins and dystroglycan s
this interaction allows signal transduction for regulation of cytoskeleton
144
how do nuclear enzymes disrupt axonal integrity
incr inflamm cytokines --\> incr ca --\> export HDAC from nucleus --\> in cytoplasm , HDAC binds the proteins that usually transport mitochondria down the axon
without mitochondria at distal axon, get axonal death
145
BDNF in neurodegenerative diseases
alzheimers - incr early , reduce as progression;
parkinsons - delivery of BDNF rescued SN dopa
huntingtons - decr amt
146
REST
inhibits BDNF transcription
Wild type huntington keeps REST in cytoplasm --\> prevents REST from inhibiting BDNF
mutant huntington --\> REST not kept in cytopalsm --\> REST enters nucleus --\> REST Inhibits BDNF --\> bad
mutant huntingtin = reduced funtion and reduced trasnport in both directinos
147
what are the ways huntingtin affects BDNF
decr transcription
decr transport
148
strategies to restore BDNF
many fancy ones, but really --\> diet, exercise, cogntiive stimulation
149
name the layers of SVZ
start at lateral ventrical
ependymal layer, gap region, astrocyte ribbon, myelin layer, striatum
source of **neurogenesis in adult CNS**
150
what makes up the adult subventricular zone
migrating neuroblasts
astrocytes
transitory amplyfying progenitor cell
ependymal cells
151
chromatin becomes more/less compact with methyl groups
MORE compact
results in reduced expression of inhibitors of myelinaiton
thus, methylation is required for remyelination
152
where are neuronal progenitors
ventricular subependymal dentate gyrus
153
glial progenitors
subcortical white matter
154
where are progenitor cells found in the subventricular zone
gap region
155
what is NO made from
arginine
156
does NO need vessicles
NOPE!
157
what way do endocannabinooids work
they act in retrograde fashion, flosting back to the presynnaptic terminal and suppressing the release of glutamtate (Excitatory)
similar effects true at GABA (inhibitory) synapses
158
what do endocannabinoids derive from?
lipid
159
CB2
receptor for endocannabinoids that are largely found on cells of immune system
160
CB1
endocannabanoid receptor that is found in brain; inhibitory GPCR ; inhibits votage gated calcium channels or stimulates K+ channels
aka has inhib action
161
