New experiences, DNA damage and Alzheimer’s disease

Experiences as seemingly unobtrusive as exploring a new environment, increase brain activity and can cause damage to the DNA of neurons in mice reports a paper published this week in Nature Neuroscience. The research also shows that this effect is exacerbated during neurodegenerative disease.

Lennart Mucke and colleagues found that mice that are allowed to explore a novel environment exhibit a number of double-stranded breaks (DSBs) in the DNA of neurons in various brain regions, including the dentate gyrus - an area necessary for spatial memory. Many of these DNA breaks are, however, fixed within 24 hours via the cell’s DNA repair mechanisms. The authors also discovered that exposing neurons to amyloid-beta - a protein fragment that is known to accumulate in the brains of Alzheimer’s disease (AD) patients and may be a primary cause of the disease - increases the number of DSBs in active neurons. The authors report that blocking abnormal brain activity by reducing the levels of the microtubule-stabilizing protein, tau, or via application of the anti-epileptic drug levetiracetam reduced the increase in DNA DSBs in these neurons.

These findings suggest that DNA repair mechanisms are a key component of maintaining the health and stability of neurons during even relatively mundane activities and hint at another mechanism by which accumulation of the amyloid-beta protein can exacerbate neuronal stresses to potentially overwhelm the DNA repair mechanisms and lead to degeneration and disease.