Huntington's Disease: Understanding the Brain Changes

Huntington's disease (HD) is a genetic disorder that affects the brain. It mainly causes problems with movement, thinking, and mood. Let’s break down how Huntington's disease changes the brain.

1. Impact on the Basal Ganglia

• Striatum (Caudate and Putamen):
  The most important change in Huntington's disease happens in an area of the brain called the striatum.
  Here, many brain cells, especially medium spiny neurons (MSNs), gradually die.
  By the time someone starts showing signs of the disease, about 70% of these important neurons in the caudate nucleus and around 50% in the putamen have been lost.

2. Changes in the Cortex

• Cortex:
  While the striatum is mostly affected, other parts of the brain, like the frontal and temporal areas, also shrink.
  This shrinkage can reduce the size of the cortex by up to 20%.

3. Key Features of Brain Changes

• Neuron Loss and Atrophy:
  When doctors look closely at the brain, they see significant shrinkage in the affected areas, especially in the striatum and frontal cortex.
• Huntingtin Aggregates:
  One sign of Huntington's disease is the presence of unusual protein clumps inside brain cells.
  These clumps are made of a faulty version of the huntingtin protein that occurs due to repeated sections in the HTT gene. In people with HD, these repeats are usually over 36 and can go as high as 250.

4. Changes in Brain Chemicals

• Dopamine and GABA:
  There’s a big drop in a chemical called GABA, which helps control brain signals, because some of its producing neurons are lost.
  This messes up the balance between signals that excite and calm the brain's activity.
  The brain's dopamine supply, important for movement, is also affected, which adds to the movement problems.

5. Other Changes in the Brain

• Astrogliosis:
  In damaged areas, star-shaped brain cells called astrocytes become more active and grow in number. This might be their way of responding to neuron loss.
• Microglial Activation:
  There are signs of inflammation in the brain, marked by activating another type of supporting cell, called microglia.
  These activated cells can harm neurons by releasing substances that cause inflammation.

Summary

The brain changes seen in Huntington's disease involve a mix of losing important neurons, problems with brain chemicals, and unusual protein clumps.
Understanding these changes is vital for searching for new treatments for this challenging disease.