Biology subjects

DePoy, L. M.

Publications and source records attributed to DePoy, L. M..

3 recordsLinked to original sources

bioRxiv2024

Regulation of Fentanyl Reward in Male and Female Mice by the Circadian Transcription Factor NPAS2

Synthetic opioids like fentanyl are highly potent and prevalent in the illicit drug market, leading to tolerance, dependence, and opioid use disorder (OUD). Chronic opioid use disrupts sleep and circadian rhythms, which persist even during treatment and abstinence, increasing the risk of relapse. The bodys molecular clock, regulated by transcriptional and translational feedback loops, controls various physiological processes, including the expression of endogenous opioids and their receptors. The circadian transcription factor NPAS2, highly expressed in the nucleus accumbens, may have a crucial function in opioid-related behaviors. Our study found sex-specific roles for NPAS2-mediated reward behaviors in male and female mice, including in fentanyl seeking and craving. We also identified specific cell types and transcriptional targets in the nucleus accumbens of both mice and humans by which NPAS2 may mediate the impact of fentanyl on brain physiology and in opioid reward-related behaviors. Ultimately, our findings begin to uncover the mechanisms underlying circadian rhythm dysfunction and opioid addiction.

neuroscience↗

bioRxiv2022

The magnitude of sex differences in host-microbe interactions are time-of-day dependent

Circadian rhythms dynamically regulate sex differences in metabolism and immunity, and circadian disruption increases the risk of metabolic disorders. We investigated the role of sex-specific microbial circadian rhythms in host metabolism using germ-free and conventionalized female and male mice, dietary manipulations, coupled with a systems biology approach. Sex differences in circadian rhythms of genes involved in immunity and metabolism are dependent on oscillations in the microbiota, microbial metabolic functions, and microbial metabolites. Further, dietary factors modify the magnitude of sex differences in host-microbe circadian dynamics. We show that consuming an obesogenic high-fat, low-fiber diet produced sex-specific changes in circadian rhythms in microbiota, metabolites, and host gene expression, which were linked to sex differences in the severity of metabolic dysfunction. These results reveal that microbial circadian rhythms contribute to sex differences in metabolism, emphasizing the need to consider sex as a biological variable in research on microbial contributions to metabolic dysfunction. HIGHLIGHTSO_LIMicrobial circadian rhythms differ by sex. C_LIO_LISex-specific rhythms in host transcriptional networks are microbiome-dependent. C_LIO_LIDiet-induced obesity entrains new sex-specific rhythms in microbiome and host genes. C_LIO_LITiming of data collection influences magnitude of sex differences. C_LI

systems biology↗

bioRxiv2020

The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice

Circadian rhythms are commonly disrupted in individuals with depression and/or anxiety disorders. Animal studies indicate that circadian rhythm disruption can cause increased depressive and anxiety-like behavior, but the underlying mechanisms are unclear. Currently, there is conflicting evidence as to whether the master pacemaker in the brain, the suprachiasmatic nucleus (SCN), plays a key role in regulating psychiatric-related behavior. To investigate the role of the SCN in regulating depressive and anxiety-like behavior in mice, we directly manipulated the neural activity of the SCN using two chronic optogenetic stimulation paradigms. Repeated stimulation of the SCN late in the active phase (circadian time 21, CT21) shortened the period and dampened the amplitude of homecage activity rhythms. Repeated stimulation of the SCN at unpredictable times during the dark phase dampened, fragmented and reduced the stability of homecage activity rhythms. In both SCN optogenetic stimulation paradigms, dampened homecage activity rhythms (decreased amplitude) was associated with increased measures of anxiety-like behavior, but not in control mice. Increased fragmentation and decreased day-to-day stability of homecage activity also correlated with increased anxiety-like behavior. Unexpectedly the change in period of homecage activity rhythms was not directly associated with any psychiatric-related behavior. Furthermore, we did not observe consistent correlations between homecage activity amplitude and depressive-like behavior in stimulated mice. Taken together, these results indicate that SCN-mediated dampening of rhythms is directly correlated with increased anxiety-like, but not depressive-like behavior in mice. This work is an important step in understanding how specific SCN neural activity disruptions affect mood and anxiety-related behavior.

neuroscience↗