A gene believed to be a possible contributor to schizophrenia and mood disorders has different effects during fetal or early childhood development, has been found by researchers.
For the study, associate Professor Dr Mikhail Pletnikov crafted a novel mouse model in which a mutant form of the gene could be turned off by feeding the animals small amounts of the antibiotic doxycycline in their chow.
AdvertisementThe animals could get the drug directly by eating it or through their mothers during gestation. Withdrawing doxycycline turned this gene on.
Using this model, Pletnikov's team generated four groups of mice: those that expressed mutant DISC1 prenatally (Pre), those that expressed mutant DISC1 postnatally (Post), those that expressed it during both periods (Pre+Post), and those that never expressed it (NO).
When the mice were about 2 months old, the researchers put the animals through a battery of behavioral tests designed to measure characteristics similar to schizophrenia and depression in humans, such as abnormal social interactions and heightened aggression under stress, comparing these animals with "control" animals that didn't express the mutant gene.
Because previous studies have shown that male mice with mutant DISC1 have such altered traits, the researchers tested male mice in each of the groups by placing them in a cage with a normal male mouse and allowing them to mingle for 10 minutes.
They found that the Pre+Post and Post groups spent significantly less time in non-aggressive social interaction with their partners than the mice of the NO group.
Those in the Pre+Post group also demonstrated significantly more aggressive attacks on their partners than control mice that did not express mutant DISC1.
To look for behaviors reflecting depression, the mice were being made to swim in a pool, or being lifted by their tails, and were timed for how long they struggled.
Mice thought to exhibit depression-like behavior spend more time immobile than non-depressed mice.
They found that only female mice of the Post group spent significantly more time immobile in the forced swim test than mice that did not express mutant DISC1. Female mice in the Pre+Post group spent significantly more time immobile in the tail suspension test than control mice.
The study also showed that selective prenatal expression led to smaller brain volumes but mild behavioral effects, pre- and postnatal expression led to behaviors and brain alterations in male mice similar to schizophrenic humans, and postnatal expression produced abnormalities in female mice similar to depression.
The team plans to study these sex-related differences in future studies.
The findings are reported in Molecular Psychiatry.
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