BMC L8 Flashcards
PaNuclues
Cluster of neurones in brain
Ganglion
Cluster of neurones in spinal cord
Plexus
Many ganglion connected together
Name 6 neurogenative diseases
SHAPE CJD
Schizophrenia
Huntingsdon Disease
Alzheimers disease
Parkinson’s disease
Epilepsy
CJD
What is AD?
Alzheimer’s disease:
Slow, progressive, neurodegenerative disorder
Most common form of dementia
State 2 causes of AD
- Intracellular accumulation of tau proteins as NFTs, neurofibrillary tangibles
- Extracellular amyloid plaques
State the symptoms of AD
- Short term memory loss, easily missed, not diagnosed
- Long term memory loss, confusion, loss of language, irritability, agression
- Loss of bodily function
- Death, usually 7 years after diagnosis
AD diagram - brain of patient
Pay attention to:
Cortex (sulci) - shrinks
Hippocampus - shrinks - memory, spatial navigation, consolidation of info
Ventricles - expand
White matter - shrinks
In general, brain shrunken
Perirhinal cortex shrinks - memory, navigation
Entorhinal cortex shrinks - Object perception, memory
How do we distinguish Familial / Genetic AD
- Early onset <65
- Autosomal dominant
- Loss of bodily function, loss of memory, progressive aphasia
What does the cholinergic hypothesis of AD postulate?
Oldest theory, postulates loss of ACh as cause
Basis of current drug therapies
Drugs which combat ACh loss not effective
Explain the Amyloid hypothesis of AD
“Extracellular accumulation of beta amyloid plaques/deposits”
- Proteolysis of APP (amyloid precursor protein, unknown function, found in synapses) leads to formation of beta amyloid deposits
- Beta amyloid deposits accumulate as extra cellular plaques
- This is neurotoxic - toxic to surrounding neurones
Why are Downsyndrome patients likely to develop AD by age of 40?
Amyloid hypothesis of AD.
APP gene - chromosome 21
Downsyndrome patient - trisomy chromosome 21
How is APOE4 a risk factor of AD?
Apolipoprotein
Risk factor
Isoform of APP
Breaks down beta amyloid plaques
What is the role of tau protein?
Tau protein binds to microtubules and stabilises them and helps them assemble
The tau protein is phosphorylated by kinase. It then forms Tau-P. Tau-P is what binds to the microtubules and stabilises them
Tau-p is dephosphorylised by phosphatase, forming tau, so it then dissociates from microtubules causing them to diassemble
Explain the tau hypothesis
Tauopathis, abnormal phosphorylation - Hyperphosphorylation - tau phosphorylates into helical paired filaments forming NFTs
NFTs (neurofibrillary tangles) are toxic to surrounding neurones
NFTs formed in the cell early (intracellular)
NFTs formed out cell later (extracellular)
Why may the tau hypothesis be unreliable?
Because the evidence contradicts whether tau-p binds or dissociates from microtubules
How can we detect AD?
PET scan of brain
Iluminates Tau Protein and Amyloid Plaques
Different pattern for Tau protein
Tau protein - usually found in hippocampus
Explain the noradrenergic hypothesis of AD
Loss of noradrenergic neurones in locus coerulus - OCCURS IN BOTH, AD, PD
Leads to symptoms of AD
Locus coeuruleus innervates hippocampus, spinal cord, cerebellum
How can AD lead to psychiatric depression and psychosis?
Noradrenergic hypothesis:
Loss of noradrenergic neurones, therefore, loss of noradrenaline.
What is Parkinson’s Disease?
Slow, progressive, neurodegenerative disease
- Loss of cells in substania nigra - diminishing of substantia nigra
- Less dopamine produced
- Increased output from basal nuclei
- Reduced activity of thalamus
- Reduced output of cerebral cortex
- Hypokinetic disorder
What is the substantia nigra? Describe its location and function.
Linked to basal ganglia via midbrain
Crescent shaped mass of cells
Sends neurones to tissues on both side of brain
Therefore, helps control coordination and movement
Describe the structure and location of the basal ganglia.
Basal ganglia located in midbrain.
Consists of
-Striatum - Caudate nucleus + putamen
-Corpus striatum - Striatum + globus pallidus
-Subthalmic nucleus
-Substantia nigra - dopaminergic region
Explain the Lewy Body theory of PD
Lewy bodies are round inclusions of polymerised alpha synuclein proteins found in the cytoplasms of neurones in the substantia nigra
alpha synuclein found at pre-synaptic terminals, function unknown, involved in synaptic vesicles
leads to rare genetically inherited form of PD
Explain the Parkin theory of PD
Parkin - involved in degradation of proteins
Mutation to parkin leads to a more common genetically inherited form of PD
“Juvinile PD”
Autosomal recessive
Early onset (<45)
Explain dopamine replacement therapy
Treatment for PD
- L-DOPA restores dopamine levels, restores the balance
- Dopamine cannot cross BBB
- L-DOPA can
- L-DOPA is a precursor of dopamine
- L-DOPA produced by body, converted into dopamine by DOPA Decarboxylase
- issue is loses its effectiveness over time
What is Huntington’s Disease?
Mutation to single gene located in chromosome 4
Autosomal dominant
This gene codes for protein called huntingtin - found in cytoplasm of cells
Function is not clear, aids in regulation of gene expression
CURRENTLY NO EFFECTIVE TREATMENT
State the symptoms of Huntington’s Disease
Chorea - hyperkinetcis, voluntary random movements
Dementia - declining cognitive ability due to other factors than age
Death 15-20 years after onset due to
-falls
-heart disease
-pneumonia
State common symptoms of schizophrenia
- Language disorganisation - neologisms
- Delusions (thought of insertion, withdrawl)
- Absence of focus
- Hallucinations
- Agitation
State the classification of schizophrenia symptoms
positive symptoms: not normally present
-hallucinations, delusions, inability to focus, language disorganised
negative symptoms - lack of elements which are usually present in one’s life including
-emotions
-pleasure
-motivation
How can we distinguish schizophrenia on an MRI scan?
-Enlarged ventricles
-Shrunken hippocampus tissue
State the causes of schizophrenia
Genetic - disruption to embronyic brain development
Environmental
Excess dopamine = increase in positive symptoms
Low dopamine = increase in negative symptoms
State treatments for schizophrenia
Antipsychotics - drugs which surpress dopamine receptors. This reduces positives symptoms.
Psychotherapy
Social rehabilitation
Antidepressants to manage associated depression
State historic / last resort treatments for schizophrenia
Prefrontal lobe lobotomy
Electroconvulsive therapy, now only applied to one cerebral hemisphere, with muscle relaxant to prevent broken bones
Give an example of a general seizure
Absence seizures
What causes general seizures
Rythmic activity from brain stem is relayed to large areas of cortex by thalamus
What happens during an absence seizure?
Petit mal
MILD SEIZURE
Early childhood
Expression goes blank
What happens during a tonic clonic seizure?
grand mal
Loss of consciousness
Loss of bowel control
Loss of bladder control
Severe biting of tongue
Broken bones due to intense muscle contractions
What causes a partial seizure?
Cerebral cortex divided into columns
Each column = isolated / single processing unit
Has an inhibitory surround (GABAergic)
Failure of inhibitory surround of the columns (isolated processing units of cerebral cortex)
This leads to uncontrollable wave of excitation in cerebral cortex
Leads to partial seizure
Describe treatments for epilepsy
- Vagus nerve stimulators placed under skin of chest to prevent brain electrical activity from becoming chaotic
- Ketogenic diet - low carb, high fat
- Anticonvulsive drugs
- Surgery - removal of seizure focus, last resort, for partial seizures
- Prevent exposure to stimuli triggers - flashing light
