Scientists have identified a gene that may be activated to reverse symptoms of major depression such as social isolation and loss of interest.
The team found that making the SIRT1 gene inactive in excitatory neurons in male mice created symptoms of depression.
According to the study published in the journal Molecular Psychiatry, a drug that activated SIRT1, reversed the symptoms.
"It has an antidepressant-like effect," said Xin-Yun Lu, a professor at Augusta University in the US.
That means drugs that activate SIRT1 and enable the usual high level of activity of these excitatory neurons might one day be an effective therapy for some with major depression, said Lu.
The firing of excitatory neurons is definitely decreased in depression, and neurons are not communicating as they should. Problems like manic behaviour and seizures, on the other hand, indicate excessive firing.
It is hard to get excited without energy, and another of SIRT1's known roles in brain cells is regulating cell powerhouses, called mitochondria.
The scientists found that at least part of the way knocking out SIRT1 in males impacted the excitability of these normally excited neurons was by reducing the number of cell powerhouses and the expression of genes involved in powerhouse production.
The depressed behaviours they saw as a result are another indicator of SIRT1's importance in that region to mood regulation and how without it, there is insufficient excitation of neurons.
However, there was a lack of impact in female mice, even though the SIRT1 variant was first identified in a large gene study of depressed women, researchers said.
They suspect physical differences in this front region of the brain, like differences in the numbers of neurons and synapses between males and females, could help explain the sex differences they found.
The team is already working on similar sex disparities in the hippocampus, another brain region important in depression as well as other conditions like Alzheimer's.
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