Ketamine treatment induces sex-specific synaptogenic effects in the medial prefrontal cortex of stress-naïve C57BL/6J mice
Emily M Flaherty, Joseph N Mauch, Sara S Mohamed, Joseph E Saurine, Connor F Thelen
Major depressive disorder (MDD) is a debilitating neuropsychiatric disease that impacts more than 350 million individuals worldwide. A neurobiological characteristic of MDD, the atrophy of spines, most often presents itself in brain regions implicated in stress response (e.g., prefrontal cortex and hippocampus). Directly combating these neural deficits, the novel rapid-acting antidepressant drug ketamine has been shown to induce its therapeutic effects by enhancing synaptogenesis and dendritic spine formation in the male rodent brain. Despite the wealth of knowledge on the neurobiological effects of ketamine in the male brain, the effects of this drug in females are not well characterized. Published and preliminary data from our group and others indicate that female mice are behaviorally more reactive to the antidepressant-like effects of ketamine. However, the innate mechanisms underlying the female sensitivity to this rapid-acting antidepressant drug still remain elusive. A modified Golgi-Cox neurohistological staining technique was used to determine whether increases in dendritic spine density in the PFC were associated with the antidepressant-like effects of ketamine in stress-naïve female mice. It was found that a single dose of ketamine (10mg/kg) elicited a synaptogenic response in the medial prefrontal cortex of male but not female mice at three days post-injection. These findings support the notion that different brain regions and/or molecular pathways are implicated in the female antidepressant response to ketamine, and highlight the need for further studies focusing on the sex-specific neuromolecular alterations following ketamine administration.
Independent Research - Graduate
Primary Advisor's Department
Stander Symposium project
"Ketamine treatment induces sex-specific synaptogenic effects in the medial prefrontal cortex of stress-naïve C57BL/6J mice" (2017). Stander Symposium Projects. 990.