Biology subjects

Yohn, C. N.

Publications and source records attributed to Yohn, C. N..

3 recordsLinked to original sources

bioRxiv2019

Social Instability is an Effective Chronic Stress Paradigm for both Male and Female Mice

Despite stress-associated disorders having a higher incidence rate in females, preclinical research mainly focuses on males. Chronic stress paradigms, such as chronic social defeat and chronic corticosterone administration, were mainly designed and validated in males and subsequent attempts to use these paradigms in females has demonstrated sex differences in the behavioral and HPA axis response to stress. Here, we developed a social stress paradigm, social instability stress (SIS), which exposes adult mice to unstable social hierarchies for 7 weeks. SIS effectively induces negative valence behaviors and hypothalamus-pituitary-adrenal (HPA) axis activation in both males and females. Importantly, while there were effects of estrous cycle on behavior, this variability did not impact the overall effects of SIS on behavior, suggesting estrous does not need to be tracked while utilizing SIS. Furthermore, the effects of SIS on negative valence behaviors were also reversed following chronic antidepressant treatment with fluoxetine (FLX) in both males and females. SIS also reduced adult hippocampal neurogenesis in female mice, while chronic FLX treatment increased adult hippocampal neurogenesis in both males and females. Overall, these data demonstrate that the SIS paradigm is an ethologically valid approach that effectively induces chronic stress in both adult male and adult female mice.

neuroscience↗

bioRxiv2018

Dentate Gyrus Activin Signaling Mediates the Antidepressant Treatment Response

Antidepressants that target monoaminergic systems, such as selective serotonin reuptake inhibitors (SSRIs), are widely used to treat neuropsychiatric disorders including major depressive disorder, several different anxiety disorders, and obsessive-compulsive disorder. However, these treatments are not ideal because only a subset of patients achieve remission. The reasons why some individuals remit to antidepressant treatments while others do not are unknown. Here, we developed a paradigm to assess antidepressant treatment resistance in mice. Treatment of mice with either chronic corticosterone or chronic social defeat stress effectively induces increased negative valence behaviors. Subsequent chronic treatment with the SSRI fluoxetine reverses these behavioral changes in some, but not all, of the mice, permitting stratification into persistent responders and non-responders to fluoxetine. We found several significant differences in expression of Activin signaling-related genes between responders and non-responders to fluoxetine in the dentate gyrus, a region that we recently reported is critical for the beneficial behavioral effects of fluoxetine. Furthermore, enhancement of Activin signaling in the dentate gyrus converted behavioral non-responders into responders to fluoxetine treatment more effectively than commonly used adjunctive antidepressant treatments, while inhibition of Activin signaling in the dentate gyrus converted responders into non-responders. Taken together, these results demonstrate that the behavioral response to FLX can be bidirectionally modified via targeted manipulations of the dentate gyrus and suggest that molecular- and neural circuit-based modulations of dentate gyrus may provide a new therapeutic avenue for more effective antidepressant treatments or adjunctive therapies.

neuroscience↗

bioRxiv2018

Fluoxetine effects on behavior and adult hippocampal neurogenesis in female C57BL/6J mice across the estrous cycle

Some mood disorders, such as major depressive disorder, are more prevalent in women than in men. However, historically preclinical studies in rodents have a lower inclusion rate of females than males, possibly due to the fact that behavior can be affected by the estrous cycle. Several studies have demonstrated that chronic antidepressant treatment can decrease anxiety-like behaviors and increase adult hippocampal neurogenesis in male rodents. However, very few studies have conclusively looked at the effects of antidepressants on behavior and neurogenesis across the estrous cycle in naturally cycling female rodents. Here we analyze the effects of chronic treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac) on behavior and adult hippocampal neurogenesis in naturally cycling C57BL/6J females across all four phases of the estrous cycle. Interestingly, we find that the effects of fluoxetine on both behavior and adult hippocampal neurogenesis are driven by mice specifically in the estrus or diestrus phases of the estrous cycle. Taken together our data is the first to illustrate the impact of fluoxetine on brain and behavior across all four stages of the murine estrous cycle.\n\nHighlightsO_LIChronic fluoxetine reduces anxiety-like behaviors in naturally cycling female mice\nC_LIO_LIChronic fluoxetine increases adult hippocampal neurogenesis in naturally cycling female mice\nC_LIO_LIThe effects of chronic fluoxetine on behavior and adult hippocampal neurogenesis are driven by the estrus and diestrus phases of the estrous cycle\nC_LI

neuroscience↗