New Method for Treating Depression

In an effort to find better depression treatments, researchers at University of California San Diego School of Medicine discovered that inhibiting an enzyme called Glyoxalase 1 (GLO1) relieves signs of depression in mice.

Depression affects at least one in six of us at some point in our lifetime, and better treatments are urgently needed. Image credit: tasnimnews.com (CC BY 4.0)

"Depression affects at least one in six of us at some point in our lifetime, and better treatments are urgently needed," said senior author Abraham Palmer, PhD, professor of psychiatry and vice chair for basic research at UC San Diego School of Medicine.

Palmer and team unraveled a previously underappreciated molecular process that can influence mouse models of depression. Here's how the process works: Cells generate energy. In doing so, they produce a byproduct. That byproduct inhibits neurons and thus influences various behaviors.

Typically, the enzyme GLO1 removes this byproduct, but inhibiting GLO1 can also increase the activity of certain neurons in a beneficial way. In mice, Palmer and others have shown that more GLO1 activity makes mice more anxious, but less was known about the system's effect on depression.

The researchers used several different antidepressant tests. They compared responses in three groups of mice: 1) untreated, 2) treated by inhibiting GLO1, either genetically or with an experimental compound, and 3) treated with Prozac, a selective serotonin reuptake inhibitor commonly used to treat depression.

The first tests they used were the tail suspension test and the forced swim tests, which are often used to determine whether or not a compound is an antidepressant. In this case, the answer was yes.

The other tests -- chronic forced swim test, chronic mild stress paradigm and olfactory bulbectomy -- are well-established measures that can also be used to measure how long it takes for an antidepressant to take effect.

In each of these tests, inhibiting the GLO1 enzyme reduced depression-like symptoms in five days, whereas it took 14 days for Prozac to have the same effect.

Palmer and team are already working with medicinal chemists at UC San Diego to develop drugs that target GLO1. (Tasnim News Agency)

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