A mouse with postpartum depression?

Researchers have developed a transgenic mouse model for postpartum depression which hints at medical interventions for the mood disorder, according to a study published this week in linkurl:__Neuron.__;http://www.neuron.org/ "For the first time we have a linkurl:useful model;http://www.the-scientist.com/2007/7/1/44/1/ to look at therapeutic interventions," said first author Jamie Maguire from the University of California, Los Angeles (UCLA). Postpartum depression is thought to be caused when

By | July 30, 2008

Researchers have developed a transgenic mouse model for postpartum depression which hints at medical interventions for the mood disorder, according to a study published this week in linkurl:__Neuron.__;http://www.neuron.org/ "For the first time we have a linkurl:useful model;http://www.the-scientist.com/2007/7/1/44/1/ to look at therapeutic interventions," said first author Jamie Maguire from the University of California, Los Angeles (UCLA). Postpartum depression is thought to be caused when the high levels of reproductive hormones plummet just after birth. Researchers have shown that hormone levels and the expression of receptors that respond to these hormones fluctuate throughout the ovarian cycle. These receptors, called GABA-A receptors, are comprised of five interchangeable subunits, which have different effects depending on their combination. The GABAnergic system has long been associated with a number of psychiatric disorders such as panic disorder and post traumatic stress disorder. When Maguire and coauthor Istvan Mody, also from UCLA, tracked the receptors' expression in pregnant and postpartum mice, they found that two GABA-A receptors, one containing the subunit delta and the other containing gamma-2, were downregulated during pregnancy. The expression increased once again shortly after birth. This pattern of expression suggested that receptors are downregulated during the hormone surge of pregnancy, and upregulated when hormone drops postpartum in order to maintain homeostatic levels. They speculated that a defect in expression of this receptor could be one explanation for postpartum depression. To test their idea, researchers created a transgenic mouse model in which the gene coding for the GABA-A receptor containing the delta subunit was knocked out in either one or both alleles. Among the many GABA-A subunits, receptors with the delta subunit are more sensitive to neurosteroids such as estrogen and progesterone. The knockouts exhibited signs of postpartum depression shortly after giving birth, such as abnormal nest building and separating themselves from pups in the nest; the mouse moms also tended to neglect or cannibalize their pups. Researchers have studied mice lacking other hormone receptors important for maternal behavior, such as estrogen-alpha receptor and oxytocin, but "we think that postpartum depression is unique," to the delta subunit containing receptor, said Maguire. The duo also showed that they could partially reverse the effect by pharmacologically activating the GABA-A delta subunit receptor in the single allele knockout. Though the results are suggestive, the receptor may not play the same role in humans. While post-pregnancy hormonal fluctuations are well established in humans, the expression pattern of GABA-A receptors and the role of the delta subunit are not known. "We think that we may have found __one__ mechanism important in postpartum depression," said Maguire, adding that she would like to try pharmacologically activating the receptor subtype in clinical trials. However there may be other mechanisms which are also important in human postpartum depression, she said. "The human condition is much more complex."
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