Brain Disorders

A2 Biology Unit 5 Topic 8

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The Brain depends heavily on synapses
Any of the 5 stages of
synaptic transmission can
be affected by drugs or by
an insufficiency in
neurotransmitter
Neurotransmitters
dopamine and serotonin
are only found in the brain
and an imbalance can
cause mental and
physical symptoms
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Parkinsons Disease
Caused by loss of nerve cells in substantia nigra that
release neurotransmitter dopamine
Cells from substantia nigra connect with frontal
cortex, brain stem and spinal cord involved in
coordination of movement
Symptoms not apparent until 80% of dopamine
producing cells have been lost
Occurs rarely in younger people genetic link
Usually in people over 50 years some link with
exposure to toxins, herbicides and pesticides

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Symptoms of Parkinsons Disease
Tremor starts in one hand
Slow movements
Stiffness of muscles, making movements difficult
Poor balance
Difficulty in walking
Problems with sleeping
Depression
Problems with breathing and speech
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Treatment for Parkinsons Disease
There is no cure, symptoms can be treated
There are problems getting drugs across the blood
brain barrier
Levo-dopa (L-dopa) precursor of dopamine.
Allows remaining functional cells to make as much
dopamine as possible. Gradually becomes less
effective
Dopamine agonists bind to dopamine receptors
and mimic effect of dopamine
MAOB inhibitors inhibit monoamine oxidase B
that breaks down dopamine
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New Treatments for Parkinsons Disease
Gene Therapy
Parkinsons disease is not a genetic disorder
May be helped (in the future) by inserting genes to
prevent dopamine producing cells from dying
Adding genes to enhance dopamine production
There are difficulties in safely inserting healthy
genes into the midbrain
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Stem cell Therapy and Parkinsons Disease
Aims to produce embryonic stem cells to replace
faulty dopamine producing cells
There are risks of uncontrolled growth and resultant
cancers
There are ethical issues associated with the use of
embryonic stem cells
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Depression
Causes not fully understood, but neurotransmitter
serotonin appears to be involved
Serotonin is the neurotransmitter in a group of cells
in the brain stem that link with cortex, cerebellum
and spinal cord
Lack of serotonin results in fewer nerve impulses in
the brain, brain activity is supressed
Depression can be triggered by circumstances or
simply by a change in brain chemistry
Neurotransmitters dopamine and noradrenaline
may also be involved
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Genetics and Depression
Gene 5-HTT involved
Linked to serotonin
production
20% of population have
short form of gene, more
likely to suffer from
depression
Homozygous long form
of gene least likely to
have depression
Heterozygous
(intermediate) form
intermediate risk
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Cellular Mechanisms and treatment
Short form of gene results in insufficiency of production of
reuptake protein that takes serotonin back into the
presynaptic membrane
People with long form of the gene produce more reuptake
protein
More reuptake of serotonin reduces concentration in
synaptic cleft, increases level of post synaptic action
potentials
Most successful drug for depression, SSRIs selective
serotonin reuptake inhibitors actually inhibit these uptake
proteins contradictory as this is opposite to predictions
TCAs (tricyclic antidepressants) work by increasing levels of
serotonin and noradrenaline
Monoaminoxidase inhibitors inhibit enzymes that break
down serotonin and other neurotransmitters
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Ecstasy and other brain enhancing drugs
Caffeine slow the rate of dopamine reabsorption at
synapses
Ecstasy is stimulant increases heart rate
Ecstasy is psychtropic changes persons perception of
the world by affecting serotonin synapses
Ecstasy blocks serotonin reuptake channels
It also moves all serotonin from presynaptic knob in to the
cleft floods post synaptic membrane with impulses
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Effects of Ecstasy
Increased heart rate, raised blood pressure and
irregular heart beat
Reduced desire to drink leading to hyperthermia
Can lead to death
Can affect hypothalamus resulting in release of
more ADH, stops kidneys producing urine
This is a problem if person continues drinking to try
to keep cool, results in osmotic destruction of body
cells
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Long term use of ecstasy causes brain damage
Areas of the brain involved with serotonin
neurotransmitters have reduced ability to
bind with serotonin
Dutch study showed loss of serotonin axons
in the thalamus and normal levels in cerebral
cortex
Some studies suggest no adverse effect
ecstasy users outperformed non drug users
in some tests. Research used squirrel
monkeys where brains may be different from
humans
Possible therapeutic effects of ecstsy are
being investigated
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Pharmacogenomics
Previously drugs have been developed to suit the majority of
people
An extension of the human genome project is looking at the
biomedically relevant variations in the human genome that
could be used to produce drugs for individual gene types
Some genetic factors effect the efficiency of some drugs
Kappa-opioid pain killers effective for women, not for men
Pale skinned red haired women are more responsive to
common painkillers
Ibuprofen has little effect in pain relief during second half of
the menstrual cycle
Fine details of human genome mean that better drugs can
be developed that target cancer cells or particular pathogens
but do not affect body cells
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Human Genome Project can be used in selecting
best drugs for purpose
Access to patients genome could save hospitals a lot of
money
Large scale study in Liverpool showed that 6.5% of
admissions were due to adverse drug reactions!
Median hospital stay was 8 days, more than 20 people in the
study (of 18,820 patients) died
1000 people die each year in the UK die from adverse drug
reactions
Others had permanently damaged organs
Advances in pharmacogenomics could improve this situation
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Choosing the right dosage of drugs
Pharmacogenomics can be used to identify people
susceptible to drug overdoses
Cytochrome P450 gene codes for liver enzymes
that break down certain drugs
Some people have less active or inactive forms of
the gene and would be very vulnerable to a drug
overdose
People with the less active or inactive form of the
gene should be excluded from drug trials
Read HSW on pages 250 and 251 and comment
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