Biochem- Neuropsychiatric disorders Flashcards
What are the major clinical findings in myastenia gravis?
- drooping eyelid
- trouble swallowing
- fatigue
- blurred vision
**-recurrent muscle weakness ofter exercise **
Are men or women affected more by MG?
Women (3:2)
What nerves are chiefly affected? What is the treatment?
- CN
- Achestylcholinesterase inhibitors
Most cases of MG have serum antibodies against what?
N1 acetylchline receptors
What is the form of MG with antibodies against the E subunit? How about the gamma subunit?
- slow channel syndrome
- Neonatal MG (transient)
What drug is typicall used to test for MG?
Edrophonium: a short acting AChEi
What is Diisopropylflurophophate?
-an irreversible AChEi (toxic nerve gas)
Wha are some of the major symtoms of huntington disease?
- Choreatic movements
- death of certain neurons
- Death ~15 years after onset
What is the genetic dominance of huntington disease?
Autosomal dominant
Neurons in the _____ ______ die and are replaced by _____ ______ in huntington disease.
- Corpus striatum
- Glial cells
A gene on chromosome __ encodes for a protein called _________. A repeat of ____ in this gene results in huntington disease.
- 4
- huntingtin
- CAG trinucleotide
Huntington disease displays _______, which means that subsequent generations contract the illness at a younger and younger age.
Anticipation
The altered gene product huntintin results inthe excess release of what excitatory NT?
Glutamate
What are the five important excitatory channels stimulated by the exces glutamate?
- NMDA
- AMPA
- Kainate
- L-AP4
- metabotropic
***the first four are cationic channels, the fifth stimulates the increase of IP3 and DAG which then stimulates cationic channels***
What kind of toxin is glutamate known as?
-Excitotoxin
What is the major treatment for the control of huntington disease?
-Bezodiazepines which increase GABA and reduce the choratic movements and seizures.
What is the role of glutamate in a stroke patient?
Induction
- Ischemia causes **glutamate to be released from oxygen starved neurons **
- Glutamate binds to NMDA
- This causes a release of calcium to toxic levels
_Amplification _
-This continues as intracellular calcium causes the release of gutamate from the NMDA stimulated cell which contiues on to excite another neuron.
_Expression _
-activation of Ca dependant nucleases, proteases and phospholipase causes degrdation of cell components and death
How does the expression step of glutamate excitotoxicity further cause ischemic damage?
Degrdation of phopholipids leads to the formation of platelet-activating factor** and the release of **arachdonic acid
–>both cause vasoconstriction, worsening the thrombosis
How does the production of arachadonic acid in glutamate excitotoxicity lead to more cell damage?
-Arachdonic acid metabolism to eicosanoids lead to the production of free oxygen radicals which damage cell components further
What is the siginificance of GABA receptors in alcohold withdrawl?
-Overactivation of GABAA receptors can lead to down regulation resulting in seizures.
What are some characteristic signs of parkingson disease?
Tremors
Bradykinesia
Rigitidy
Degeneration of the ____ _____ and the _____ _____ results in parkinson disease.
- Substantia Nigra
- Corpus Striatum
Decreased levels of _____ and increased levels of _____ are observed in parkinson disease>
- Dopamine
- Acetylcholine
After a loss of ____-____% of nigral cells, symtons of parkinson disease appear.
-80-90%
What histological abnormaility is seen in the SN of parkinson patients?
Lewy Bodies
What are the six steps in the dopamine pathway?
- sythesized from tyrosine
- stored in vesicles
- released via exoxytosis
- Binds to one of 5 receptors
- Reuptake by ATP transporter
- Degraded in the synaptic cleft of after reuptake by MAOB–> homovanillic acid
What are the three treatment stratagies to managing parkinson disease?
- Increase the synthesis of dopamine by giving L-DOPA
- Block the degredation of dopamine
- Use dopamine receptor agonists
Why is L-DOPA given as a treatment and not straight dopamine on the rocks?
L-DOPA can cross the BBB
What two classes of drugs are used to block the degradation of dopamine?
- MAO-Is
- COMT-Is
Both work to increase the dopamine concentration in the synaptic cleft
What is the name of a dopamine receptor agonist?
Bromocriptine
What are the names of the two MAO-Is that are important?
- Deprnyl
- Selegiline
(if you don’t take your MAOI you will be in deep shit)
Is there an identified genetic component to parkinson disease?
NO
What is a dug that can exacerbate parkinson disease by inhibiting dopamine storage?
Reserpine
What is a neurotoxin that can destroy dopamine secreting cells?
Street heroin–> MPTP
Do MAO-Is potect against MPTP damage? What is the significance?
Yes. Can prevent future progession of PD.
Why is it good to give cabidopa with L-Dopa in the treatment of PD?
-Carbidopa inhibits dopa decarxylase. This prevent dopa decarboxylase from converting L-Dopa to DA which does not cross the BBB
What are some common characteristics of Alzheimer disease?
- Onset generally> 65y
- Progressive cognitive impairment accompanied by affective and behavioral disturbances
- First sign is loss of memory–> final stage of incapacitation
What are the two difinitive histological features of Alzheimer disease?
-Amyloid ß peptide Neurofibrillary plaques and tangles
What microtube associated protein is hyperphosphorylated in neurofilbrillary plaques and tangles?
tau
What two structures degenerate the most in Alzheimer disease?
-cortex and hippocampus
What is the amyloid cascade hypothesis?
Amyloid b-protein, a peptide fragment of a transmembrane protein, is insoluble in the extracellular space.
-AbP may be neurooxic by stimulating excessive calcium uptake leading to activation of protein kinase and Tau–> cell death
Whart are some characteristics of schizophrenia?
-psycotic symptoms: disturbances of thinking, feeling and behavior.
What are positive symptoms of schizophrenia?
Hallucinations, delusions and bizzare behavior
what are negative symptoms of schizophrenia?
Social withdrawl, emotional blunting
What are some noted strcutural abnormalities in schizophrenic patients?
- Altered orientation of hippocampal pyramidal cells
- enlarged ventricles
What is the dopamine hypothesis with respect to schizophrenia?
Hypoerdopaminergia detected by:
- elevated dopamine in brain tissue
- elevated homovanillic acid (HVA) in CSF
- elevated numbers of D2 receptors in brain tissue
what is the modified dopamine hypothesis?
there is abnormal, not necessarily excessive, dopaminergic activity in schizophrenia.
