HMB200H1 Study Guide - Final Guide: Phencyclidine, Excitotoxicity, Movement Disorder
1. What are the symptoms of schizophrenia? Explain how each cluster of symptoms
may have a different neural mechanism.
Positive symptoms: hallucinations, delusions, disorganized speech
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Negative symptoms: lack of emotion, impaired social interaction
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Cognitive deficits: impaired attention, memory and executive function
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2. What changes in the brain are often observed in schizophrenia? Describe what
properties of the brain change (e.g. gray matter, brain activity) and how these
properties change (e.g. increase/decrease).
Reduces overall cortical mass and hippocampus/ amygdala size and
enlarged ventricles.
Thinning of orbitofrontal cortex, dorsolateral prefrontal cortex and
hippocampus
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Loss f GABA neurons (parvalbumin-expressing GABA neurons)
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Gray matter loss in temporal cortex and dorsolateral prefrontal cortex
○
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3. Explain the gender differences in schizophrenia. What is one reason these
differences may be evident?
Male: earlier onset of SZ
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Female: later onset of SZ (estrogen level goes down)
Reasons of differences different interaction of genetic and
environmental factors between genders
○
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4. What are some genetic factors related to schizophrenia? What are some
environmental factors?
Genetic factors: genes like DISC1, GAD1, NRG1 etc.
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Environmental factors: adolescent use of cannabis, maternal depression,
winter time birth, malnutrition etc.
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5. Why might adolescent cannabinoid use be a risk factor for schizophrenia?
Excessive stimulation of CB receptor during a critical developmental period
can lead to Schizophrenia. Cannabis use is associated with lower white
mater integrity ad gray matter reduction in hippocampus and prefrontal
cortex
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6. What is the evidence for the dopamine hypothesis of schizophrenia?
In SZ there is higher levels of D2 receptors, and too much dopamine causes
positive symptoms, thus reducing dopaminergic transmission would be
therapeutic in SZ
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Reducing DA activity with antipsychotic drugs reduces positive symptoms of
the disorder. Negative symptoms are not well explained in the DA
hypothesis
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7. What is the evidence for the glutamate hypothesis of schizophrenia?
Antagonizing NMDA receptors (ketamine and phenylcyclidine) produces SZ-
like symptoms. Post-mortem studies show reduced levels of NMDA on
certain cells. This suggests that positive and negative symptoms of SZ might
involve NMDA receptors
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8. Explain how variations in the NRG1 gene are linked to schizophrenia risk.
NRG1 may increase the activity of DA neurons ad transmission in 2 ways
Increase glutamate receptor activity in DA neurons
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Decrease glutamate receptor activity in GABAergic neurons that
inhibit DA neurons
○
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9. Describe the role of GABA and GABA neurons in schizophrenia.
GABA is necessary in inhibition. In SZ, variation in the GABA synthesizing
enzyme GAD1 (glutamic acid decarboxylase) may be a risk factor. Disruption
in PV-and CCK- GABA neurons in hippocampus and PFC may contribute to
SZ symptoms
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10.How is the DISC1 gene associated with schizophrenia?
Disrupted in Schizophrenia 1 gene produces a protein that is generally
involved in neuronal proliferation, differentiation and migration. Therefore,
dysfunction can affect neurodevelopment and lead to SZ symptoms
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11.Explain coup and counter-coup forces in head impacts. Be able to use these
forces to predict patterns of brain injury following head impacts.
Coup (at impact) / counter-coup ( opposite impact)
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12.What are some general symptoms of chronic traumatic encephalopathy (CTE)?
There are 4 stages.
Attentional deficits, confusion, disorientation, dizziness1.
Memory loss, social deficits, impulsive behavior, poor decision making2.
Movement disorder, speech difficulty, sensory difficulty, tremors,
suicidal, depression
3.
Dementia 4.
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13.Describe the neuropathology in CTE. Differentiate this pathology from that in
Alzheimer’s Disease.
Hyperphosphorylated tau tangles spread throughout brain. Amyloid B and
TDP43 deposition is observed, there is axonal degeneration and white
matter degeneration, Neuroinflammation, neuronal loss and BBB
disruption.
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Difference in CTE & AD is seen in the spread and onset of location. While AD
spares the cerebellum, CTE ultimately affects the cerebellum
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14.The blood brain barrier may be disrupted in CTE. Why is this a problem? How
might we test for evidence of this disruption?
BBB breakdown leads to neurotoxic factor accumulation, faulty transport,
inflammation and immune response, and ultimately neurodegeneration
through injury and synaptic /neuronal loss. Evidence may bee seen in
presence of S100B, an astrocytic protein in blood serum
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15.What are some biomarkers for CTE?
Exosomal tau, CCL11 and N-acetylaspertate
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16.Differentiate hemorrhagic and ischemic stroke.
Hemorrhagic stroke due to weakened blood vessel ruptures causes causes
bleeding in brain
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Ischemic stroke due to blood clot (fat deposit) that interrupt the blood flow
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17.Describe the main arterial systems in the brain. Use this knowledge to predict
injury. 18.Describe the cellular events that occur following hypoxia. Be aware that
these events are inter-related and overlap in time!
Following hypoxia: ionic change -> secondary messenger -> mRNA->
protein -> inflammation-> recovery
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19.Why do ionic imbalances occur in stroke? Give several reasons!
Na+/K+ exchanger, Ca2+ ATPase and Na+/Ca2+ exchanger. If Na+/K+
exchanger doesn't function then the Na+/Ca2+ exchanger will not function
either, leading to higher intracellular calcium.
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20.Which ion regulation mechanisms in the cell depend upon ATP? Why is the role
of ATP important in the case of stroke?
Na+/K+ ATPase, Ca2+ ATPase reply on ATP. ATP is important as it allows
energy dependent ion movement
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21.Describe glutamate transporters. Where are these transporters expressed?
The glutamate transporters (GLT1) are Na+ dependent. When there is
insufficient Na+, transporter cannot clear glutamate from the extracellular
space effectively and this lead to further increases in glutamate levels. The
transporters are expressed on astrocytes
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22.Which types of receptor channels are involved in glutamate excitotoxicity?
NMDA receptors are involved in excitatory (specifically the GluN2B subunit)
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23.What type of drugs might be used to mitigate brain damage in ischemic stroke?
Tissue plasminogen activator (t-PA) can dissolve the clot to improve blood
flow
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24.What type of post-stroke rehabilitation strategies do we have available?
Constraint-induce movement therapy
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Speech therapy
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Study notes 7
Wednesday, April 4, 2018
1:33 PM
Document Summary
Explain how each cluster of symptoms may have a different neural mechanism. Negative symptoms: lack of emotion, impaired social interaction. Describe what properties of the brain change (e. g. gray matter, brain activity) and how these properties change (e. g. increase/decrease). Reduces overall cortical mass and hippocampus/ amygdala size and enlarged ventricles. Thinning of orbitofrontal cortex, dorsolateral prefrontal cortex and hippocampus. Gray matter loss in temporal cortex and dorsolateral prefrontal cortex: explain the gender differences in schizophrenia. Female: later onset of sz (estrogen level goes down) Genetic factors: genes like disc1, gad1, nrg1 etc. Excessive stimulation of cb receptor during a critical developmental period can lead to schizophrenia. In sz there is higher levels of d2 receptors, and too much dopamine causes. In sz there is higher levels of d2 receptors, and too much dopamine causes positive symptoms, thus reducing dopaminergic transmission would be therapeutic in sz. Reducing da activity with antipsychotic drugs reduces positive symptoms of the disorder.
