Midterm Slids Flashcards
1
Q
Diagnosis:
A
Distinguish one disease from another
2
Q
Etiology:
A
What caused it –> The apparent causation and developmental history of an illness
3
Q
Prognosis
A
Forecast the probably course of a disease
4
Q
Idiopathic:
A
disorder of unknown origin
5
Q
Incidence
A
the number of new cases of a disorder in the given time period
6
Q
Prevalence
A
Percentage of the population that exhibits a disorder during a specific time period
7
Q
Lifetime Prevalence
A
percentage of people who have been diagnosed with a specific disorder at any time in their lives
8
Q
What allowed neurological diseases to be properly diagnosed in the 19th century? (3)
A
- Development of tools for investigation
- Imaging techniques
- Better note taking which lead to the ability to make correlations
9
Q
What makes diagnosing a disorder so complex?
A
Many symptoms occur in many disorders and there are no conclusive causes or tests
10
Q
What 2 things are always done when trying to diagnose a disorder?
A
A complete medical history and a physical exam
11
Q
What are additional tests that can be run for diagnosis
A
- MRI
- EEG
- Lumbar puncture
- Evoked potentials
12
Q
The brain makes up _% of our body weight and take up _% of our energy
A
2
20
13
Q
How did we historically find out about what parts of the brain do?
A
By patients having brain injuries and seeing the ramifications
14
Q
What are the modern ways of determining what parts of the brain do
A
- Montreal procedure
- animal models
- brain imaging
15
Q
What part of the brain moderates most complex, higher order processing
A
Cerebral cortex
16
Q
Deep grooves in the brain
A
Fissures
17
Q
Which fissure separates the two hemispheres
A
Longitudinal
18
Q
What connects the 2 hemispheres
A
corpus callosum
19
Q
What is another word for the lateral fissure?
A
Sylvian
20
Q
What does the lateral fissure separate?
A
The frontal and parietal lobes from the temporal lobe
21
Q
CNS
A
Brain + spinal cord
22
Q
PNS
A
Somatic NS
Autonomic NS
23
Q
What is another word for the autonomic NS
A
Visceral
24
Q
What does the autonomic NS control
A
Everything outside voluntary control:
- Smooth muscles
- Secretory functions (glands
- Sympathetic and Parasympathetic NS
25
The spinal cord is responsible for what kind of movement?
Spinal reflexes
26
where is the CSF and what does it do?
In the sub-arachnoid space and it surrounds the brain and spinal cord and protects them by allowing them to float
27
What is the CSF made of?
The water, NA, Cl, and HCO3 it pulls from the blood
28
What are the functions of the CSF
- Transports substances throughout the NS
| - Removes cell waste
29
Where is the CSF made?
In the ventricles by the ependymal cells
30
What is the specific name for the cells that make CSF
Choroid plexus
31
What things cannot pass through the BBB
- Large charge
- Large size
- Lipophobic/hydrophilic
32
What cells are the primary info processing units
neurons
33
What cells support and modulate activity of neurons
glia
34
3 types of neurons
Sensory, motor, inter
35
Nociceptors:
pain receptors
36
Is it pain or motor neurons that do not need to reach the brain to do their job? Why?
Motor
| Spinal reflex
37
Where are neurons layered?
In the cortex
38
Where are neurons usually in nuclei
older parts of the brain
39
What defines a nucleus from other bundles of cells?
They are a cluster of neurons that form a functional group (use the same chemicals)
40
Organization of cortical networks, why?
Uniform and grid-like
| Because there was limited space
41
Organization or sub-cortical and brainstem networks
Sporadic and irregular organization
42
Nerve = _NS
PNS
43
Tract = _NS
CNS
44
Which matter is rich in cell bodies and blood vessels
Grey matter
45
Which matter is rich in myelin
White matter
46
The forebrain divides into what 2 parts
Telencephalon and diencephalon
47
The midbrain becomes what?
Mesencephalon
48
The hindbrain becomes what 2 parts?
Metencephalon and Myelencephalon
49
The 2 hemspheres are part of what part of the brain?
Cerebrum
50
Lateralization:
Differences (specialization) of the hemispheres
51
The left brain controls which part of the body
right
52
The left brain is lateralized for what functions
language, math and logic
53
The right brain is lateralized for what functions
emotion, spatial orientation, facial recognition, art/music
54
Commisural tracts
allow the left and right side to communicate
55
Where do most commisural tracts pass through?
corpus callosum
56
Is the corpus callosum a commisual tract?
yes
57
Projection tracts:
extend vertically between the higher and lower brain regions, to carry info between cerebrum and body
58
Association tracts
connects regions within the same hemisphere
59
What are the 2 different association tracts
Short fibers: connect gyri within a lobe
| Long Fibers : connect lobes within a hemisphere
60
2 subcortical structures
Basal ganglia and Limbic system
61
Precentral gyrus is the ___ cortex
Motor
62
Post central gyrus is the ____ cortex
Somatosensory
63
Functions of frontal lobe
problem solving
planning
emotion
voluntary motor activity
64
Functions of temporal lobe
Understanding language
memory
hearing
65
Functions of parietal lobe
Sensation
reading
body orientation
spatial sense
66
Functions of occipital lobe
vision
| colour perception
67
What are the contributions of each love to cognition
Frontal - Planning responses + personality
Temporal - recognizing stimuli
Parietal - attending to stimuli
Occipital - processing visual stimuli
68
Role of the basal ganglia (3)
control or voluntary movement, procedural memory and habit formation
69
3 main parts of the basal ganglia
Caudate nucleus + putamen + striatum
Globus pallidus
Substantia nigra
70
What are 2 things that dopamine is involved in?
Reward and Parkinson's
71
3 roles roles of limbic system
Emotion control
Learning
Memory
72
3 main parts of the limbic system
Cingulate cortex
Amygdala
Hippocampus
73
Cingulate cortex
Emotional processing and memory
74
Amygdala
Fear
Aggression
Emotionally charged memories
Decision making
75
Hippocampus
Learning and memory (short to long term)
76
Functions of the cerebellum
Balance
Coordination and control of voluntary movement
Fine muscle control
77
Brain stem
Breathing
Heart beat
Respiration
78
2 parts of the diencephalon
Thalamus and Hypothalamus
79
What is the midbrain
A small area with many important functions (substantia nigra)
80
What are the 2 parts of the hindbrain
Pons and Medulla
81
Function of pons
connects cerebellum to brainstem
| - inhibits movement during sleep
82
Function of medulla
Controls breathing and heart rate
83
Function of Tegmentum
Modulates activities like sleep, attention and reward
84
Function of Tectum
Important in linking auditory and visual systems, controls orienting movement
85
Superior coliculi =
vision
86
Inferior colicili
hearing
87
What is the most important role of the cerebellim
Fine tuning movement
88
The cerebellum is __% of the brain's volume and __% of its neurons
10
| 50
89
If you put things out of equalibrium, they will
equilibrate
90
Neurons maintain an electrical charge across their:
membrane
91
The tendancy for electrons to move represents their ability to do work and is called ___ measured in ___
Electrical potential
| Volts
92
When the channels are shut the energy is all ____ energy
potential
93
What is outside the neuron?
CSF
94
Why is the inside of the neuron negative
Because the proteins in it are negatively charged
95
Who discovered boielectricity in the late 1700s
Galvani and Volta
96
At rest is the neuron polarized
yes
97
Threshold of excitation #
-55mV
98
4 properties of an action potential
- fast
- localized but spreading
- all or nothing
- involve a large reversal of membrane polarity
99
voltage gated sodium channels open at __ and close at __
-55mV
| +30mV
100
voltage gated potassium channels open at ___ and close at ____
+30mV
| -70mV
101
How does the action potential propagate?
depolarization in one region can stimulate adjacent areas to depolarize as well
102
what ensures that action potentials only go one way
refractory period
103
action potentials happen the ___ way for all behaviour
same
104
The synapse is the site of ____ transmission in the cell
chemical
105
What is the PNS parallel to NTs?
hormones
106
How many kinds of NT
more than 50 identified
107
3 categories of NT
- Amines (dopamine, epinephrine, serotonin)
- Amino Acids (glutamate, GABA)
- Other
108
When the AP reaches the terminal, what ion enters the terminal
Calcium
109
What does calcium do in the terminal
releases the vesicles to dump NT into the synapse
110
Where can terminals connect
Anywhere
| - dendrites, soma, axon
111
2 types of post synaptic potentials
IPSPs
| EPSPs
112
What process allows the neuron to "decide" whether to fire or not
Integration of PSPs
113
NT are ____ for a specific ____
ligands
| receptor
114
Ionotropic receptor
Fast --> directly triggers ion channels to open or close
115
Metabotropic receptors
Slow --> indirectly opens or closes ion channels through second messengers
116
What are 4 ways to deactivate NTs
1. Diffusion
2. Degradation
3. Reuptake
4. Glial cells
117
Hormones:
Chemical messengers that are released by one cell group and travel through thr blood stream to act on targets
118
What are endocrine glands and 3 examples
Release hormones throughout the body
| - Testes, thyroid, adrenal glands
119
What are exocrine glans and 3 examples
Use ducts to secrete fluids outside the body
| - Sweat, lacrimal (tears) and mammary
120
8 main endocrine glands
- Hypothalamus
- Pituitary
- Thyroid
- Adrenal
- Parathyroid
- Pancreas
- Ovaries
- Testes
121
Neuroendrocrine glands
Brain regions that can release NT into the blood stream
122
What type of synapse can dump NT into the blood stream
axosecretory synapses
123
What are the 2 glands are the major locus of neuroendocrine integratoin in the body and 3 examples
Hypothalamus and Pituitary
- HPA
- HPT
- HPG
124
What are the 2 glands are the major locus of neuroendocrine integration in the body and 3 examples
Hypothalamus and Pituitary
- HPA
- HPT
- HPG
125
5 Principles of Action of Hormones
1. Act in a gradual fashion
2. Change probability or intensity of behaviour (shift in homeostasis)
3. Have a reciprocal relationship with behavour
4. May have multiple effects
5. Released in pulses or at e specific time
126
3 similarities between NT and hormones
1. neurons and glands make and store chemicals and release them upon stimulation
2. Bind to receptors that stimulate target cells
3. Some chemicals can be both hormones and NT
127
4 differences between hormones and NT
1. Local vs Distant
2. Fast vs Slow
3. Voluntary vs Involuntary
4. Precice vs Imprecise
128
What types of receptors to hormones act on?
Metabotropic
129
What is the typical progression of glands in hormone release
Hypothalamus (neurohormones) --> Pituitary (releasing hormones) --> Target Endocrine Gland (target hormone) --> Target Tissue
130
What type of hormone is usually released from the pituitary gland
releasing hormones
131
Which glad is considered the master gland
Pituitary
132
What connects the pituitary gland to the hypothalamus
pituitary stalk
133
What are the 2 divisions of the pituitary gland and how are they connected to the hypothalamus?
Anterior - blood vessels
| Posterior - directly by axons from the hypothalamus
134
What do the anterior and posterior pituitary release?
Anterior - releasing hormones (ACTH, TSH)
| Posterior - Vasopressin and oxytocin
135
What is the function of the hormones synthesized and released from the hypothalamus?
To inhibit or stimulate the release of hormones from the pituitary
136
What is another word for releasing hormones?
Tropic
137
Where are vasopressin and oxytocin synthesized?
Hypothalamus
138
How does the endocrine system regulate itself?
Negative feedback loops
139
Can a system have both a positive and negative feedback loop?
Yes
140
Steps of the HPA axis
Hypothalamus (CRH) --> Pituitary (ACTH) --> Adrenal cortex (glucocorticoids) --> Increased cortisol induces metabolic changes
141
Stressor:
A stimuli that challenges the body's homeostasis and triggers a response
142
Minor vs Major stressors
```
Minor = may be acute or chronic
Major = something that really rocks the foundation of a persons life
```
143
What 2 things does the stress response accomplish?
1. Temporarily puts the brain and body into "overdrive" in order to deal with the stressor
2. Suspends bodily repair and growth in order to conserve energy
144
What is the fast stress pathway and what does it respond to?
Sympatho-adrenomedulary axis (SAM)
| The alarm response to a surprise (acute) stressor
145
What is the slow stress pathway and what activates it?
```
Hypothalamic-pituitary axis (HPA)
Long lasting (chronic) stressors
```
146
What are the 2 adrenal glands and what do they secrete
```
Cortex = cortisol
Medulla = epinephrine and norepinephrine
```
147
What is the ratio of epinephrine and norepinephrine released
80% epinephrine
| 20% norepinephrine
148
How does the SAM axis work
Hypothalamus send projections to the spinal cord --> directly stimulates the sympathetic nervous system --> release of epinephrine and norepinephrine
149
Epinephrine and norepinephrine are ____ hormones from _____ family
Peptide
| Catecholamine
150
What receptors do epinephrine and norepinephrine bind to?
Adrenergic receptors
151
What type of hormone is cortisol
Steroid hormone
152
What receptors do cortisol bind to?
Glucocorticoid (GR) and mineralcorticoid (MR) receptors
153
What time is cortisol the highest in the body
in the morning
154
What are the 2 main areas of the body that cortisol affects?
Metabolism and immune system
155
What affect does cortisol have on metabolism (3)
- More breakdown of lean body mass (non-fat tissue)
- increased blood sugar
- less bone and connective tissue formation
156
What 3 areas in the brain are sensitive to cortisol and help shut down the stress response
- Hypothalamus
- Anterior pituitary
- Hippocampus
157
What happens to cognition when there is a stress response?
It is impaired
| >> PFC shuts down and older brain regions take control
158
What is good stress called
Eustress
159
Psychological resilience
Ability to cope with stressors improved by regularly overcoming them
160
When is it important to encounter manageable stressors
Childhood to build resilience
161
Too much stress results in what?
Learned helplessness
162
What is a way of volitionally getting good moderate stress
exercise
163
What are the physical effects of too much stress (4)
1. Increase in resting and stress induced levels of GCs
2. Increased CRH expression
3. Larger adrenal cortex
4. Less GRs in the hippocampus (decreased neg feedback ability)
164
What are the changes in the hippocampus as a result of chronic stress (3)
- Less spine density
- less neurogenesis
- impaired negative feedback ability
165
Acute vs chronic stress
```
Acute = sharpens cognition and mobilizes energy
Chronic = impairs cognition and results in fatigue
```
166
Which type of cell death always illicit an inflammatory response?
Necrosis
167
Acquired Brain Injury
any brain injury that occurs after brith (not hereditary, congenital or degenerative
168
What are 6 possible causes for ABI
- anoxia
- drug toxicity
- poisoning
- concussion
- blast injury
- penetrative trauma
169
TBi includes only trauma to the brain caused by an ____ _____ force
External mechanical
170
What is the #1 cause of death in children and youth
TBI
171
2 biggest risk factors for TBI
age and sex
172
Is a concussion a mild or severe TBI?
Mild to moderate
173
What causes damage to the brain during an injury
When there is a collision between the brain and the skull
174
What are the 3 steps of injury in TBI
1. Site where the brain and skull make first contact = coup
2. Pressure can cause the brain to rebound and contact the opposite side of the skull = contre-coup
3. This motion continues until the energy dissipates
175
What are the 3 possible directions of impact on the head
Linear, rotational or angular
| >> Usually a combo
176
Which direction of injury is worst
Rotational
| The degree of rotational force determines the severity of the injury
177
What leads to the generalized damage in the brain after an injury
The grey and white matter will move at different speeds and slide over each other
178
What is the primary phase of a TBI
Damage caused by initial impact
| Swelling and bleeding cause increased intracranial pressure
179
WHat is the secondary phase of TBI
Damage arising from the primary injury
| Energy crisis and possible infection
180
What is the only case where there can be possible infection after TBI
When there is a penetrating injury
181
What is the energy crisis
Lack of oxygen and glucose due to disrupted blood flow
182
What is the process of excitotoxicity
1. Necrosis results in excess glutamate
2. Leads to continual firing of AP
3. Results in lots of Ca in cell
4. Excess Ca goes in the mitochondria and will lead to apoptosis
183
What is the cellular damage at the site of impact of a TBI?
Necrotic cell death
| > All cell types impacted
184
What is a diffuse axonal injury
Twisting forces cause axon to me torn from cell body
185
What is another word for the axon being torn from the soma
Axotomy
186
What are the 2 things that cause the energy crisis
1. Lack of glucose (less ATP)
| 2. Lack of oxygen --> causes anaerobic glucose metabolism
187
What is the result of hypoglycaemia
Leads to cognitive deficits as neuronal activity decreases after mass excitation of exitotoxicity
188
What is the bad result of the brain switching to anaerobic metabolism
it leads to the overproduction of lactic acid --> acidosis
| >>Causes damage to BBB
189
What possible further damage could arise from damaged BBB
It is more permeable so something from the periphery can cause an infection in the brain
190
Is the brain immune privileged?
No
191
The brain is immune protected, what does that mean?
the peripheral immune system cannot get into the brain generally speaking
192
What does it mean to say that the immune system is decentralized
Immune cells circulate in the blood and act where they are needed
193
where do all immune cells develop from?
bone marrow
194
What are the 2 divisions of the immune system?
Innate and adaptive
195
The immune system relies on _____ communication through ______
chemical
| cytokines
196
Are cytokines only secreted by immune cells?
No, they are secreted by other cells too
197
What is the basal level of cytokines in relation to the basal level of hormones
Lower
198
What is the main thing that differentiate cytokines from hormones
Cytokines can increase very rapidly
199
Are cytokines pro or anti inflammatory?
There are both types of cytokines
200
Are pro or anti inflammatory cytokines more harmful?
Neither, they are both beneficial as long as they are in balance
201
What nerve provides parasympathetic innervation of heart and digestive tract
Vagus nerve
202
Paraganglia cells
The cells on the vagus nerve that releases NT upon cytokine binding
203
What nerve is the bridge between the CNS and PNS
Vagus nerve
204
What cell type is the first on the scene when there is an immune response in the brain
Microglia
205
What method does microglia use to clean up debris in the brain
Phagocytosis
206
What type of cytokine do microglia secrete
pro-inflammatory
207
Other than cytokines, what molecules do microglia secrete?
Neurotrophic Factors (promote cell survival)
208
Microglia come in 2 forms. What are they and what do they mean?
```
Star = nothing is wrong
Ball = something is wrong
```
209
What is another word for reactive oxygen species
Free radicals
210
What makes reactive oxygen species
Regular cell metabolism
211
When are ROS produced more?
During stress (like injuries)
212
What is oxidative stress?
When there are more ROS than antioxidants
213
What negative effects can ROS have on neurons
Can kill neurons
| >>Disrupts the DNA, membrane and proteins
214
Do people always lose consciousness when they get a consussion?
No
215
How many concussions go unreported
25%
216
Prior concussions _____ the likelihood of a second concussion and cause greater _____
increase
| morbidity
217
Repeated concussion have ______ effects, even if they are separated by years
cumulative
218
What is CTE
Chronic Traumatic Encephalopathy
| It is a progressive degenerative disease found in individuals with a history of multiple concussions
219
Is CTE a concussion?
No, it is a distinct disease
220
What brain changes are associated with CTE (4)?
- lower brain weight
- widespread atrophy
- enlarged ventricles
- tau aggregates and beta-amyloid plaques
221
What are common symptoms of CTE?
- memory impairments
- depression
- impulsive behaviour
- suicidal thoughts and/ot behaviours
222
What 2 sources of blood does the brain use?
Common carotid
| Vertebral arteries
223
The brain arteries form a common circles at the base of the brain called?
Circle of Willis
224
What is the overlap of the arteries in the brain like?
Limited
225
Stroke is the ___ leading cause of death
2nd
226
Ischemia
Lack of blood flow to tissue or organ
227
Stroke
interruption of blood flow to the brain
228
2 types of stroke
```
Ischemic = blockage in blood vessel
Hemmorhagic = rupture in blood vessel
```
229
What stroke is most common
Ischemic 80%
230
Large vs small vessel thrombosis (ischemic)
```
Large = blockage in one of the larger blood supply arteries
Small = blockage in one of the smaller, but deeper, arteries
```
231
What causes stroke (3)
1. Narrowing of the artieries in the neck or brain (plaques)
2. Genetic mutations
3. Environmental/experiential factors (high BP, smoking, trauma)
232
What is the common link between all causes of stroke?
Inflammation in the blood vessel walls
233
What are the symptoms of stroke
Depend on the location of stroke
234
A stroke where results in ataxia and motor problems
Cerebellar
235
What is a rare but mostly fatal stroke region
brain stem
236
Even though it is less common there are more _____ with hemorrhagic strokes
death
237
What is the mortality rate of intracerebral hemorrhage
35%
238
The swelling and increased pressure of a hemorrhage leads to what
cell death
239
What are subarachnoid hemorrhages most often caused by? What is the mortality rate?
Aneurysm
| 40-50%
240
Characteristics of a mild stroke
- Transient ischemic attack
- brief loss of perfusion
- may affect whole brain or be region specific
241
Characteristics of severe stroke
- Global ischemia
- complete loss of perfusion
- often fatal
242
Transient Ischemic Attack (TIA)
"mini stokes"
| Causes and symptoms the same as strokes but they are shorter
243
TIA come when in 15-13% of patients who have a severe stroke
Before
244
How are TIAs protective
The brain gets to adapt to the lack of blood and oxygen more slowly. Can prime the brain for a larger later stroke
245
What is the treatment for TIA
Anti-coagulants (blood thinners) to prevent clotting and a larger stroke
246
Why is a stroke so serious?
Because the blood needs a constant supply of glucose and oxygen and it does not store its own
247
How long can the brain go without oxygen before permanent cellular damage?
4 minutes
248
Infarction
Ischemia-induced cell death
249
Core of a stroke
The area directly fed by blocked vessel
| <20% blood flow
250
Penumbra of stroke
Outskirts of blockage still getting blood from other vessels
20-40% blood flow
251
Apoptosis is caused by a lack of ____, why?
glucose
| Cannot fuel Na/K pump --> glutamate rushes in --> excitotoxicity and exhaustion cause cell to self-destruct
252
Necrosis is caused by a lack of ____, why?
Oxygen
Brain switches to anerobic metabolism --> acib build up, --> increases membrane permeability --> water rushes in --> cell bursts
253
The core has what type of cell death
apoptosis and necrosis
254
The penumbra has what type of cell death, why?
Apoptosis
| Receiving the diffused death signals the dying cells from the core are sending out
255
Should research focus on the core or the penumbra?
Penumbra, the core is a lost cause
256
When there is a stroke the BBB is weakened. What does that mean for re-perfusion
Peripheral immune cells can enter the brain and exacerbate the swelling
257
The heightened immune response that results from the weakened BBB can impede what?
recovery
258
The increase in Ca after a stroke is bad in what 2 ways?
1. Triggers release of more Glu (excitotoxicity)
| 2. Results in the produciton of ROS
259
When there is too much Ca for the cell to handle, what happens?
The mitochondria triggers apoptosis
260
Collateral circulation
the blood flow through secondary pathways after the obstruction to the principle pathway occurs
261
Survival of the stroke affected region depends on (4)
- degree of obstruction
- How suddenly it happened
- length of time without blood
- degree of available collateral circulation
262
What is the more important factor in the survival of the stroke brain region
Degree of collateral circulation
263
What is the immediate treatment of an ischemic stroke (2)
TpA - clot buster
| Neurothrombectomy - surgical removal of the clot
264
Within what time period does TpA work
3-4.5 hours
265
Do people recover after a stroke
Most people recover at least a portion of their neurological function
266
How far can nearby neurons migrate to make up for cell death after a stroke?
5mm
267
Axonal sprouting after a stroke
the axon makes new branched off connections to the surviving neurons
268
Angiogenesis
vascular growth
269
What does speech and physical therapy after a stoke facilitate
neuroplasticity
270
Common impairments after a stroke (3)
Motor - upper limb use and might need an assistive device for walking
Cognitive - memory, learning, language
Sensory - tingling or pain
271
Anosognosia
When you have something wrong with you but you do not know it
272
Hemi-spatial neglect
Patients completely ignore one side of the world
273
Which side most often gets neglected in hemineglect
Left side from right parietal damage
274
pairs of chromosomes
23
275
Proteins DNA gets wrapped around
histones
276
What do histones help with
Control the activity of genes
277
Alleles
variants of a gene
278
Expression of any train depends on _______ production
protein
279
3 roles of proteins
Structural
Enzymatic
Cell signalling
280
Epigenetics changes the _____ of DNA
accessability
281
Huntingtin is what type of disorder
heritable
282
What pattern of inheritance does huntingtin follow
autosomal dominant
283
The huntingtin gene is on what chromosome
4
284
Huntingtins symptoms appear
mid 30s-40s
285
Prevalence of huntingtins
5-10/100 000
| >Most common inherited neurodegenerative disorder
286
Short form for the huntingtin protein
htt
287
Where is the huntingtin protein expressed
Everywhere in the CNS and peripheral tissues
288
What is the normal htt protein called
Wild type (WP)
289
When is the WT htt protein critical
Embryonic development
290
The htt protein has repeats of what codon
CAG
291
How many CAG repeats is ok and how many is huntingtin
```
<35 = normal
36-40 = uncreased risk
>40 = Huntington will develop
```
292
What is wrong with excess repeats of the CAG codon
It changes the conformation of the protein, leading to mis folding and toxic protein aggregates in the cell
293
Can a deficincy in WT htt produce HD
no
294
What combination of htt genes is necessary to produce HD
Increased mutant htt and loss of WT htt
295
What are the symptoms of HD
progressing motor, cognitive and emotional symptoms
296
Motor symptoms of HD
Chorea
Clumsiness
Repetative movements
297
Cognitive symptoms of HD
Restlessness
Agitation
Lack of concentration
Short term memory problems
298
Emotional symptoms of HD
Depression and apathy
| Antisocial behaviour and aggression
299
When do the emotional symptoms of HD start
Several years before the onset of motor symptoms
300
What is the progression of the HD symptoms?
Usually gets wrose
301
After a while the HD chorea subsides and starts to look more like ______
Parkinson's (hypokinesis)
302
Progressive dementia and death occur __ yeard after HD onset
15-20
303
Neurons in what part of the brain are affected in HD
Basal ganglia and cerebral cortex
304
Basal ganglia neurons are mostly
inhibitory
305
2 pathways basal ganglia influences movement
Direct -->excitation of motor neurons --> movement
| Indirect --> inhibition of motor neurons --> suppresses movement
306
In HD, the neurons in the cortex that project to which 2 parts are most at risk
Motor cortex and limbic system
307
Where in the cell is the htt protein foud
cytoplasm
308
Intraneural inclusions
when the mutant htt accumulates on the nucleus of the neuron
309
Aggregates of the htt are correlated with death in the ____ but not in the ______
cortex
| striatum
310
Its not the accumulation of the aggregates that causes cell death in HD but rather the
translocation of aggregates to the nucleus that induces pathology
311
Where do aggregates in HD accumulate more quickly? What might this do?
Nucleus
| Might alter gene expression
312
How do the aggegates form in HD
The cell will recognize the mutated protein and cut it up. the cut up pieces will clump together
Can also be the result of abnormal splicing
313
Is the molecular directionality of HD known?
No
314
Why might the striatum be more at risk for HD damage than other brain regions?
Increased risk because of all the Glutamate projections to this brain region
>>>higher excitotoxicity risk
315
Long circuit loop implicated in HD
Basal ganglia-thalamo-cortical circuitry
316
What NT is involved in HD? How is it affected?
GABA
| 80-90% decrease in GAD (GABA precursor)
317
Why can dysregulated GABA be problematic in HD
Increase in GABA + Glu in the corticalstriatal circuit --> Disruption in the integrative processes by medium spiny neurons
318
Why might there be an increase in GABA in HD?
To deal with the increase of Glu as a result of cell death
319
Increase in ____ NT receptor stimulation may contribute to symptoms of HD
Glutamate (NMDA receptor)
320
Excitotoxicity in HD might also result from a decrease in glial _____ of glutamate
uptake
321
Is there a cure for HD?
No, it is fatal
322
What is the treatment for HD
Symptom management
323
Where do upper motor neurons originate
In the brainstem or motor cortex
324
Lower motor neuron send messages to muscles and tell them what?
to start contracting
325
Upper motor neurons have what 2 jobs
1. Tell the lower motor neurons to carry start signals to the muscles
2. Tell LMN when to stop sending signals to contract (end movement)
326
Upper motor neurons can talk to LMT directly and indirectly, how?
```
indirect = Interneurons
Direct = UMN to LMN
```
327
Upper motor neurons cannot leave the
CNS
328
Where are the cell bodies of the LMN
Brain stem or spinal cord
329
Can the axons of LMN leave the CNS
Yes
330
What are the 2 types of LMN
Spinal or cranial
331
UMP can pass through what two regions via what pathways to synapse with the LMN
Brainstem = corticobulbar tract
| Spinal cord = corticospinal tract
332
How is the corticobulbar pathway protected from complete loss of function from damage
Some of the neurons stay on the ipsilateral side and some decussate
333
Damage to UMN and LMN can both lead to what?
weakness
334
What happens when there is damage to the upper motor neurons? (5)
```
Spasticity
hypertonia
Hyperreflexia
clonus
Babinski reflex
```
335
Why do we see those symptoms when there is damage to the UMN
Without inhibition, the LMN keeps telling the muscles to contract and this leads to sustained contraction and rigidity
336
Why do we see the symptoms with LMN damage?
The LMN are unable to tell the muscles to start contracting, so the muscles are flaccid
337
What symptoms are seen n LMN damage (5)
```
Flaccidity
Hyporeflecxia
Hypotonia
Muscle atrophy
Fasciculations
```
338
Upper motor neurons release what NT
glutamate
339
lower motor neurons release what NT
Acetylcholine
340
Is the cause for ALS known
No, it is idiopathic
341
What is the mean age of diagnosis for ALS
~60
342
What is the pattern of heredity for the familial form of ALS
Autosomal dominant
343
The gene abnormalities of ALS lead to what?
protein aggregates
344
ALS involves degredation of what
Upper and lower motor neurons
345
What type of movement is damaged in ALS
Voluntary movement
346
When muscles are not used they _____
atrophy
347
Sensory neurons in ALS
they are not affected, people can still feel
348
What does ALS not affect
```
Sensation
Heart
Digestion
Bladder
Internal organs
Cognitive processes
```
349
What is the only voluntary movement that people with ALS can do
Move their eyes
350
Where does weakness of ALS typically start
Arms or legs
351
Loss of ___ function occurs first with sporadic ALS
| Loss of ____ function occurs with familial ALS
arms
| legs
352
What are the later symptoms of ALS
loss of ability to:
- walk
- speak
- hold up head
- swallow
353
There is an increased risk of what with ALS. What does this often lead to
Aspiration
| Leads to infection, is often fatal
354
What is the average life expectancy of ALS once diagnosis
2-5 years
355
Is there a cue for ALS
no
356
The only drug for ALS does what?
Slows the loss of muscle strength by blocking sodium channels and reducing glutamate release
>> decreases excitotoxicity
357
Other than drug, what are the 3 therapies for ALS
Physical - exercise and strength to keep mobility for as long as possible
Occupational - redesign environment
Speech-Language pathologist - keep speech and swallowing for as long as possible
358
General pathology of Upper and lower motor neurons
Upper - spasms, hypertonia and hyper reflexia
| Lower - muscle atrophy and fasciculations
359
Necroptosis
Programmed necrosis
360
Astrocytes in ppl with ALS
have been shown to release toxins that induce necroptosis
361
What happens when you put motor neurons in a petri dish with ALS astrocytes
What type of study is this
they start dying
| >> in vitro
362
Underlying issues of how to fix astrocytes from killing motor neurons
How do astrocytes become toxic
| How is this happening in vivo
363
What does the drug Riluzole try to do in ALS
Block sodium channels to prevent neurotoxicity
364
Under neormal circumstances, what do astrocytes do to protect neurons?
Via what ?
Remove excess glutamate
Glutamate transporters
365
In ppl with ALS, what was discovered about the glutamate transporters on glial cells
there were less of them
366
What are 5 ways we can experience what it is like to have ALS
1. eat with a fork holding 10lb
2. Sit, moving nothing but eyes
3. Use wheelchair in store without speaking
4. Climb 2 stairs at a time with weight on ankles
5. talk with marshmallows in mouth
367
Dementia
a set of symptoms that are caused by disorders that affect the brain
368
Symptoms of dementia (4)
memory loss
Problems with thinking
problem solving problems
Language problems
369
Does dementia affect daily life
yes
370
Is dementia a specific disease?
no, it is caused by many things
371
Neuron difference between dementia and normal aging
Normal aging = dysfunctioning of neurons
| Dementia = dying neurons
372
4 behavioural differneces between normal aging and dementia
Normal aging vs Dementia:
1. Forgetting convo or event from last year vs forgetting recent events and convos
2. Forgetting names of aquantences vs. forgetting lames of family and friends
3. Occasional difficulty finding words vs frequent pauses and word substitutions
4. Person worries but not family vs family worried but not person
373
What is the leading cause of dementia
Alzheimers
374
Mild cognitive impairment =
memory problems greater than expected for age, but does not impair daily function
375
What puts people at greater risk for AD. What is it also known as?
mild cognitive impairment
| >>dementia
376
Mild AD (5)
- memory loss
- other cog deficits
- impaired daily function
- depression
- apathy
377
Moderate AD (3 main categories)
- Impairment: language, reasoning, sensory processing, conscious thought
- Unable to learn new things or do complex tasks
- Hallucinations or paranoia
378
Severe AD (4)
- Massive cell loss
- completely dependent
- cannot communicate
- body shuts down
379
Cognitive And functional abilities in AD
Changes in ability to think, understand, remember and communicate
380
Emotions and mood in AD
- Apathy, depression and anhedonia
| - withdrawl from people
381
Behaviour in AD
- Out of character behaviours
- restless
- repetative
382
Physical abilities in AD
Impaired coordination and mobility influence ability for daily tasks
383
2 forms of AD
Sporadic and familial
384
Causes of sproadic AD
Unknown but age is biggest risk factor
385
What gene (and number) is associated with sporadic AD
APOE e4
1 allel = risk
2 alleles = higher risk
386
What does APOE do?
Helps break down a protein called beta amyloid which forms aggregates in AD
387
Casue of familial AAD
A dominant gene that speeds up the progression of the disease
388
What other disease is highly comorbid with AD
Down syndrome
389
When can AD be diagnosed for sure
After death
390
Degradation starts where in the brain in AD and spreads where
Hippocampus
| spreads to rest of cortex
391
4 structural signs of AD
- brain atrophy
- narrow gyri
- wide sulci
- enlarged ventricles
392
2 key pathological features of AD
Beta amyloid plaques
| Neurofibrillary tanges
393
Beta amyloid plaques do what in in brain
illicit immune response
| Collect around blood vessels, weakening them and increases the risk of hemorrhage
394
Beta amyloid plaques increase the risk of what
hemorrhage
395
Fibrillary tangles lead to what
dysfunctional axons which causes apoptosis
396
Microglia in AD
Usually they take up amyloid plaques, but they are also activated by plaques, so they initiate an immune response and cause damage
397
Astrocytes in AD
Start to atrophy, cause excitotoxicity, and contribute to the inflammatory response
398
ROS in AD
they build up during normal aging and makes the brain more vulnerable to oxidative stress
399
Is there a cure for AD
No cure and no treatment to stop or delay symptoms
400
What is a main issue for making drugs for AD
Need something that can cross BBB
401
What is the prognosis for AD
Death within 8-10 years of onset
402
How do people with AD usually die
infection
403
Can we prevent AD
No
| But good nutrition, physical activity and stimulating brain can help you stay healthy
404
Our ability to develop effective therapies is limited by
our understanding of the disease
