1.2 Explain changes in the brain that cause Parkinson’s disease to develop

This guide will help you answer 1.2 Explain changes in the brain that cause Parkinson’s disease to develop.

Parkinson’s disease is a progressive neurological condition. It affects movement, balance, and coordination. It develops as a result of specific changes in the brain. These changes mostly involve the death of certain nerve cells and problems with a chemical messenger called dopamine. This guide covers the main processes so that you can understand how the brain changes lead to symptoms.

Role of Dopamine in the Brain

Dopamine is a chemical messenger. The brain uses dopamine to transmit signals between nerve cells. It is important for smooth, controlled movement. Without enough dopamine, movements become slow and stiff. Tremors, muscle rigidity, and problems with balance can occur.

In a healthy brain, dopamine-producing nerve cells are found in an area called the substantia nigra. This is part of the midbrain. These cells send dopamine to another brain area called the striatum. The striatum is part of the basal ganglia. The basal ganglia are responsible for planning and controlling movement.

When Parkinson’s disease develops, these dopamine-producing cells gradually die. This means the brain cannot produce enough dopamine. The lack of dopamine disrupts the normal balance of signals in the brain’s motor system.

Loss of Dopaminergic Neurons in the Substantia Nigra

The most significant change in the brain in Parkinson’s disease is the loss of dopaminergic neurons in the substantia nigra pars compacta. These neurons manufacture and release dopamine. They also contain pigment called neuromelanin, which gives the substantia nigra its darker colour.

When these neurons die:

• Less dopamine is available in the striatum
• Coordination of movement becomes impaired
• Messages between the brain and muscles are disrupted

The loss of these cells develops over years. By the time visible symptoms appear, around 50 to 70% of dopaminergic neurons are already damaged or dead.

Impact on the Basal Ganglia Circuit

The basal ganglia control movement by a network of brain circuits. Two pathways play a main role:

• Direct pathway – helps to start movement
• Indirect pathway – helps to stop unwanted movement

Dopamine balances these pathways. It stimulates the direct pathway and reduces activity in the indirect pathway. This means movement can start smoothly and unwanted movement can be stopped.

Without enough dopamine:

• The direct pathway becomes less active
• The indirect pathway becomes overactive
• As a result, it becomes hard to start movement and control its speed

This imbalance causes bradykinesia (slowness of movement) and rigidity.

Lewy Bodies and Protein Build-up

A key feature seen in the brains of people with Parkinson’s disease is the presence of Lewy bodies. Lewy bodies are abnormal clumps of protein found inside nerve cells. They mainly contain a protein called alpha-synuclein.

In Parkinson’s disease:

• Alpha-synuclein changes shape and clumps together
• These clumps interfere with how nerve cells work
• Over time, they may contribute to cell death

Scientists believe that faulty handling of alpha-synuclein by the brain’s cleaning systems plays a part. The protein build-up might spread from one nerve cell to another, affecting wider brain regions.

Mitochondrial Dysfunction

Neurons are highly active cells. They need a lot of energy to function. Mitochondria are the parts of a cell that produce energy. In Parkinson’s disease, mitochondria in dopaminergic neurons can become damaged. Damaged mitochondria produce less energy and can leak harmful molecules called free radicals.

This can lead to:

• Oxidative stress, which damages proteins, DNA, and cell membranes
• Reduced ability of cells to repair themselves
• An increased rate of cell death

Mitochondrial problems combined with oxidative stress speed up the loss of dopamine-producing neurons.

Neuroinflammation

Inflammation is the body’s way of responding to injury. In Parkinson’s disease, the brain’s immune cells, called microglia, can become overactive. Overactive microglia release chemicals that damage neurons.

Neuroinflammation can:

• Harm healthy neurons nearby
• Make existing damage worse
• Interfere with recovery processes

This persistent inflammation creates a toxic environment for dopamine-producing cells.

Changes in Other Brain Chemicals

While dopamine loss is the main cause of movement symptoms, other brain chemicals are also affected in Parkinson’s disease.

These include:

• Acetylcholine – important for balance and coordination
• Serotonin – affects mood and emotional control
• Noradrenaline – helps regulate attention and automatic functions like blood pressure

Changes in these chemicals may explain non-movement symptoms such as depression, anxiety, sleep problems, and memory changes.

Spread of Pathology in the Brain

Researchers have observed that Parkinson’s disease doesn’t only affect the substantia nigra. Changes can begin in other parts of the nervous system, like the olfactory bulb (linked to the sense of smell) and the lower brainstem.

The Braak staging theory explains that:

• Early changes often occur in smell and sleep-related brain areas
• Changes then move to the substantia nigra and motor control pathways
• Later, they may spread to higher brain areas involved in thinking and memory

This is why symptoms such as loss of smell and sleep disorders can appear years before movement problems.

Genetic and Environmental Influences on Brain Changes

Most cases of Parkinson’s disease are not directly inherited. Yet, in some people, specific genetic changes can increase risk. These genes often control proteins involved in mitochondria, protein handling, and cell protection.

Environmental factors may also increase the chance of these brain changes. Examples include:

• Long-term exposure to pesticides
• Some metals in high amounts
• Head injuries

These factors might trigger stress in dopamine-producing neurons, making them more likely to die.

Example of How Brain Changes Cause Key Symptoms

Tremor
Loss of dopamine affects the timing signals in motor circuits. This can cause alternating activity in muscles that produces shaking.

Rigidity
Increased activity in the indirect pathway keeps muscles more tensed than normal, making movement stiff.

Bradykinesia
The reduced stimulation of the direct pathway slows down all voluntary movements.

Postural instability
Changes in dopamine and acetylcholine pathways disturb balance control.

Long-Term Progression of Brain Changes

In early stages, only part of the substantia nigra is affected. Over time, more cells die and dopamine levels drop further. The striatum then receives too little dopamine to keep movements fluid.

Later, changes spread to other brain areas:

• The limbic system, which regulates mood and behaviour
• The cortex, which controls thinking and voluntary action
• The brainstem, which controls automatic bodily functions

This spread explains why more symptoms appear over time, including speech problems, swallowing difficulties, cognitive decline, and autonomic dysfunction.

Final Thoughts

Parkinson’s disease develops because of a mix of linked brain changes. The most important is the gradual loss of dopamine-producing cells in the substantia nigra. This loss upsets the balance of motor control pathways, leading to the main movement symptoms. At the same time, harmful protein build-up, mitochondrial damage, and inflammation make the damage worse. Over time, these changes spread beyond movement areas of the brain, giving rise to more complex symptoms.

Understanding these changes helps health and social care workers to see why treatments focus on replacing or mimicking dopamine and protecting neurons. It also explains why care planning needs to adapt as the disease progresses. By knowing what is happening in the brain, you can better support individuals with Parkinson’s disease in their daily lives.