Brain chemistry and drugs (8.14, 8.15, 8.16, 8.17, 8.18)
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Good brain health requires both neural connectivity and the correct chemical environment. The right chemicals must be present at the right levels and in the right locations to preserve normal brain function.
Key chemicals associated with brain health are dopamine and serotonin.
Serotonin is a neurotransmitter linked to mood. It is produced by groups of neurons along the brain stem with axons extending across a large portion of the brain. When serotonin levels are below the normal range, mood is also lower.
If the rate of serotonin reuptake is greater than the rate of serotonin release, the level of serotonin will drop.
Depression is a multifactorial condition with both “nature” and “nurture” elements. There are several genes linked to susceptibility alongside many environmental triggers.
Treatment plans for depression involve both drugs and lifestyle changes.
Drug-based treatments for depression are commonly based on SSRIs, selective serotonin reuptake inhibitors, which slow the rate at which serotonin is removed from the brain, allowing the base level to be maintained at a higher concentration.
Lifestyle changes include:
- regular exercise
- stress reduction
- healthy diet
- better sleep patterns.
Dopamine is a neurotransmitter released by neurons in the midbrain. The axons extend throughout the cortex, the brain stem and the spinal cord.
When dopamine levels are too low, neural transmission is slow and less effective.
When dopamine levels are too high, brain activity becomes “chaotic”. Excess dopamine is linked to schizophrenia and can be caused by the use of drugs such as cocaine.
Parkinson’s disease occurs when dopamine–secreting neurones in the basal ganglia die. The axons from these neurones connect to the motor cortex.
Individuals with Parkinson’s disease have low dopamine levels in their motor cortex, resulting in reduced signal transmission. This is observable as:
- muscle stiffness
- slowness of movement
- muscle tremors
- issues with balance and walking.
Parkinson’s disease can be treated by:
- Reducing the rate of dopamine breakdown through enzyme inhibition.
- Introducing a dopamine precursor, L-dopa, which forms dopamine in the bloodstream.
- Introducing a dopamine antagonist which mimics the action of dopamine on receptors.
- Deep brain stimulation (DBS) of the basal ganglia to encourage dopamine production.
The recreational drug MDMA, found in ecstasy, causes increased levels of serotonin in the brain over a short period of time.
SSRIs, used to treat depression, are carefully developed to produce a gradual and sustained reduction in the reuptake of serotonin, resulting in a controlled change in the baseline brain chemistry.
When MDMA is consumed:
- The presynaptic membranes become temporarily blocked.
- Serotonin levels rapidly build in the synaptic cleft.
- The drug is metabolised, and the serotonin level rapidly decreases.
- Serotonin deficit in the neurones slows the rate at which the normal level can be reestablished.
MDMA therefore produces a mood spike (euphoria, heightened senses) followed by an extreme low.
MDMA also impacts other brain functions, such as temperature and heart rate control, which can be fatal.
DNA sequencing can be used to determine the sequence of base pairs in an organism’s genome.
The Human Genome Project successfully sequenced the first complete human genome. Since then, thousands of human genomes have been sequenced.
Only about of the human genome is made up of coding DNA, which directly codes for proteins. The remaining 98 of the human genome is non-coding DNA, which does not directly code for proteins, but has other useful functions.
The proteome consists of all the proteins produced by an organism’s genome.
Pre-mRNA contains introns and exons. Each gene can code for multiple different proteins when the pre-mRNA is spliced in different ways prior to translation.
Proteomics can aid in understanding how genes code for multiple proteins, depending on how the pre-mRNA is altered.
Sequencing human genomes has identified various single nucleotide polymorphisms (SNPs), which are common inherited genetic variants. These are the cases where one base has been replaced by another. SNPs may or may not have observable impacts.
Some SNPs are associated with the development of certain diseases, such as dementia or Alzheimer’s disease.
Other SNPs can be associated with how people respond to drugs.
As DNA sequencing becomes more accessible, genetic factors such as disease risk and drug response are becoming easier to predict.
There are social, moral and ethical issues around DNA sequencing.
There are ethical considerations around who owns and accesses genetic data. Patents can be taken out on human DNA for novel and industrial applications.
Genetic testing could lead to discrimination in employment, and in health or life insurance. People may have variants which are associated with an increased risk of a certain disease, but never develop the disease.
If genetic testing becomes even more accessible, people may learn their disease risk or whether they are a carrier of a certain disease without receiving genetic counselling or support.
Genetic engineering involves manipulating an organism’s genome. One of the most common ways this is carried out involves inserting desired genes into a bacterial plasmid, creating recombinant DNA.
This recombinant DNA can be inserted into an organism, creating a transgenic or genetically modified organism.
Gene insertion is possible as transcription and translation are universal biological processes.
Following extraction, the desired gene is placed into a vector, which is usually a bacterial plasmid.
The plasmid is edited to contain two markers: one is a selectable marker, such as a gene conferring antibiotic resistance, and the other is a detectable marker, such as a fluorescent marker or an enzyme that changes colour under specific conditions.
The plasmid is opened at the same site as the marker genes using a restriction endonuclease. DNA ligase joins the plasmid and the desired gene together. This results in one of the marker genes failing to function.
The functional markers allow screening to determine which bacteria have taken up the desired gene.
Once the recombinant vector has been produced, it must be transferred into the target organism. If the target cell is a bacterial cell, each cell must independently take up the plasmid.
Bacterial cells can subsequently be used to transfer the genetic material into a eukaryotic cell.
An alternate method for insertion of a recombinant vector into a eukaryotic cell is the use of gold or tungsten particles, coated with the plasmid and fired at the target cell using a gene gun. The eukaryotic cell can then incorporate the plasmid into its genome and express the desired gene.
Following the take-up of the successfully recombinant plasmid shown above, the host bacteria will exhibit antibiotic resistance but will not fluoresce. The bacteria are then allowed to multiply on an agar plate infused with antibiotics. This allows only the correct bacteria, the non-fluorescent spots, to be extracted and grown to create the cell culture.
Animals can be genetically modified to produce drugs and proteins, this is called pharming.
Mammals, such as sheep and goats, can be genetically modified so that proteins, such as proteins involved in clotting, are produced in their milk. These proteins can then be purified and used medicinally to treat conditions such as haemophilia.
Genetically modified plants can be produced using the bacteria Agrobacterium tumefaciens. This bacterium causes tumour growth in plants. Rapid mitosis in tumours can be utilised to transfer desired genes into plant cells.
Plants can be modified to be resistant to weed killers, such as glyphosate, or to produce their own insecticides.
