Missing Brain Enzyme Leads to Abnormal Levels of Fear in Mice, New Research Reveals

Fear is a vital response to physical and emotional danger—if we didn't feel it, we couldn't protect ourselves from legitimate threats. But new research from neuroscientists and molecular biologists at University of Southern California shows that a missing brain protein may be the culprit in cases of severe over-worry, where the fear perseveres even when there's nothing of which to be afraid.

Researchers examined mice without the enzymes monoamine oxidase A and B (MAO A/B), which sit next to each other in our genetic code as well as on that of mice. In their prior research they found an association between deficiencies of these enzymes in humans and developmental disabilities along the autism spectrum such as clinical perseverance (the inability to change or modulate actions along with social context).

They compare mice without MAO A/B with their wild-type litter-mates. both type of mice were put in a new, neutral environment and given a mild electric shock. All mice showed learned fear the next time they were tested in the same environment but with the MAO A/B knockout mice displays a greater degree of fear.

But while wild mice continued to explore other new environments freely after the trauma, mice without the MAO A/B enzymes generalized their phobia to other contexts — their fear spilled over onto places where they should have no reason to be afraid.

The mice without MAO A and MAO B also learned eye-blink conditioning much more quickly than wild mice, which has also been noted in autistic patients but not in mice missing only one of these enzymes.

Researchers found that the mice without MAO A/B did not display any differences in learning for spatial skills and object recognition, but in their ability to learn an emotional event, the [MAO A/B knockout mice] are very different than wild types.

When both enzymes are missing, it significantly increases the levels of neurotransmitters, which causes developmental changes, which leads to differential expression of receptors that are very important for synaptic plasticity — a measure of learning — and to behavior that is quite similar to what we see along the autism spectrum.