1. Neurotransmitters in the Brain

2. What are the different neurotransmitters in the brain? Currently, over 60 different molecules meet the criteria for being a neurotransmitter Neurotransmitters can be classified in terms of their chemical compositions: ● Amino acids: e.g GABA, Glutamate ● Purines: e.g ATP, Adenosine ● Gasotransmitters: e.g Nitric Oxide ● Amines: e.g Acetylcholine, Adrenaline ● Peptides: e.g Vasopressin, Endorphins ● In the brain, the main types of neurotransmitters are amino acids, amines and peptides. Some neurotransmitters such as GABA are always inhibitory, some such as glutamate are always excitatory, and some such as dopamine can act as both an inhibitory or an excitatory neurotransmitter. If it often the receptor on the post-synaptic neurone which determines if a neurotransmitter is excitatory or inhibitory.

3. Sympathetic and Parasympathetic Nervous Systems The sympathetic and parasympathetic nervous systems are divisions of the peripheral nervous system (the division of the nervous system not including the spinal cord or brain). ● Sympathetic Nervous System: ● Can be said to have the generalised function of rapidly responding to external stimuli, such as controlling the 'fight-or-flight' response. This is typically done through the up- and down- regulation of certain homeostatic mechanisms e.g by inhibiting peristalsis in the digestive tract and increasing the rate and force of heart beats. Redirection of blood flow away from the organs in the gastrointestinal tract and towards muscles which may need to be engaged ● Regulates the release of adrenaline ● Acetylcholine is the neurotransmitter for synaptic transmission ● Nerves originate from the 'thoracolumbar' region (radiate from the thoracic vertebrae)

4. Parasympathetic Nervous System: ● Has the generalised function of stimulating the 'rest and digest' activities of the body, including promoting digestion, defecation, salivation and sexual arousal ● Parasympathetic responses are typically slower and inhibitory ● Mainly uses acetylcholine as a neurotransmitter, but peptides are also used ● Nerves radiate from the cranialsacro areas (the upper lower regions of the spinal cord ● The PSNS is not considered antagonistic to the SNS, but rather complementary

5. Parkinson's Disease Parkinson's Disease is the second most common neurodegenerative disease behind Alzheimer's Disease ● PD affects 0.3% of the total population, ● and 1% of people over 60 ● Most symptoms affect motor systems, with the most common symptoms being rigidity, akinesia/bradykinesia, tremor and a shuffling gait ● The disease is progressive and there is no cure ● The vast majority of cases are idiopathic in origin

6. Mechanism of Parkinson's The symptoms of Parkinson's Disease arise due to the degeneration and death of dopaminergic neurones in an area of the brain known as the substantia nigra. Normally, dopamine has a modulatory effect on the motor systems that initiate and inhibit movements. Dopamine is analogous to a dial. ● Dopamine can strengthen excitatory signals to the motor cortex to ease the initiation of voluntary movements. ● Dopamine also inhibits the inhibition of movements so movements can be slowed but not stopped (e.g returning to walking after running, rather than just stopping) ● With a decrease in dopamine concentrations due to the loss of dopaminergic neurones, the initiation of movements is made much more difficult, hence the akinesia. The 'freezing' that many Parkinson's patients suffer from is due to the inability to control the slowing of movements ●

7. Non-drug Treatments for Parkinson's There is no cure for Parkinson's Disease, but there are treatments available beyond the most common prescription drug, L-DOPA: ● Deep brain stimulation (DBS) involves the implantation of a neuralstimulator ('brain pacemaker') into a nucleus of the basal ganglia (involved in voluntary motor control). Although the mechanism of action is not fully understood, the periodic electrical signals emitted by the neuralstimulator can very effectively control the main motor symptoms of Parkinson's: ✔ Can be effective in mitigating/reducing the motor symptoms of the disease, which can also reduce dependence on medications ✗ Only suitable for mid-stage Parkinson's patients, with no sign of mental dysfunction or signs of cardiovascular disease ✗ Risk of infection or bleeding during surgery, as well as rejection by the body ✗ Risk of incorrect neural interactions to cause neuropsychiatric side effects ranging from apathy and depression, to personality changes and hypersexuality. However, recalibration may fix these

8. Monoamine oxidase inhibitors: ● Drug therapy which increases dopamine availability by inhibiting enzymes involved in dopamine metabolism. Dopamine therefore remains for a longer time period in the synaptic cleft ✔ Effective for minor improvements in motor symptoms in early stage Parkinson's Disease, with few side-effects as a monotherapy ✔ Can be used throughout the disease to aid the action of other medications such as L-DOPA ✗ Has less of an effect than L-DOPA, especially in later stages ✗ Can produce adverse side-effects such as nausea and depression ✗ Increases the likelihood of experiencing side effects from other medications like L-DOPA, such as dyskinesia (uncontrolled, jerky movements)

9. Depression Depression is a mental disorder, characterised by low mood. Patients are affected in different ways, but symptoms can include feelings of hopelessness and low self-esteem, or a loss of enjoyment from previously enjoyable activities. Anxiety is also common. At its most serious, it can lead to self-harm and suicidal thoughts It is thought that the neurotransmitter serotonin can be involved in depression. People with depression have lower serotonin concentrations in their blood, so it is assumed this is also true for the brain. Areas of the brain associated with sleep and mood typically use serotonin as a neurotransmitter.

10. Treatments for Depression Treatments for depression generally involve both a medical prescription and a talking therapy. Talking therapies can include counselling, whereby past traumatic events are discussed and the difficult feelings the patient experienced can be explored. Cognitive behavioural therapy (CBT) involves looking at the present and future to change the way a patient will think about and cope with future problems.

11. Antidepressants Antidepressant drugs typically belong to class of drugs known as selective serotonin reuptake inhibitors (SSRIs). The exact mechanism of action is unknown, but it is known that the end result is an inhibition of serotonin reuptake. After being released into the synaptic cleft by the presynaptic neuron, SSRIs work to inhibit the reuptake of the neurotransmitter back into the presynaptic neuron. Receptors on the postsynaptic neuron may therefore be bound to multiple times to trigger multiple action potentials.

12. Any questions?