Skip to main content

BRIEF RESEARCH REPORT article

Front. Behav. Neurosci.
Sec. Pathological Conditions
Volume 18 - 2024 | doi: 10.3389/fnbeh.2024.1445184

Parkinson's LRRK2-G2019S risk gene mutation drives sex-specific behavioral and cellular adaptations to chronic variable stress

Provisionally accepted
Christopher A. Guevara Christopher A. Guevara 1Kumayl Alloo Kumayl Alloo 2Swati Gupta Swati Gupta 1Romario Thomas Romario Thomas 1Pamela Del Valle Pamela Del Valle 1Alexandra R. Magee Alexandra R. Magee 1Deanna L. Benson Deanna L. Benson 1*George W. Huntley George W. Huntley 1*
  • 1 Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, United States
  • 2 Department of Biological Sciences, Columbia University, New York City, New York, United States

The final, formatted version of the article will be published soon.

    Anxiety is a psychiatric non-motor symptom of Parkinson's that can appear in the prodromal period. Parkinson'srelated anxiety affects females more than males. How stress, anxiety and Parkinson's are related and the basis for a sex-specific impact of stress in Parkinson's are not clear. We addressed this using young adult male and female mice carrying a G2019S knockin mutation of leucine-rich repeat kinase 2 (Lrrk2 G2019S ) and Lrrk2 WT mice. To assess within-sex differences between genotypes in stress-induced anxiety-like behaviors in young adulthood, we used a within-subject design whereby mice underwent tests of anxiety-like behaviors before and following a 28 day (d) variable stress paradigm. There were no differences in behavioral measures between genotypes in males or females at baseline. Following stress, male G2019S mice were affected similarly to male wildtypes except for novelty-suppressed feeding, where stress had no impact on G2019S mice while significantly increasing latency to feed in Lrrk2 WT control mice. Female Lrrk2 G2019S mice were impacted similarly to wildtype females across all behavioral measures. Post-stress analyses compared cFos immunolabeling-based cellular activity patterns across several stress-relevant brain regions. The density of cFos-activated neurons across brain regions in both male and female Lrrk2 G2019S mice was generally lower compared to stressed Lrrk2 WT mice, except for the nucleus accumbens which in male Lrrk2 G2019S mice, cell density was significantly higher than all other groups. These data suggest that the Lrrk2 G2019S mutation differentially impacts anxiety-like behavioral responses to chronic stress in males and females that may reflect sex-

    Keywords: Anxiety, Depression, Mice, Open-field, Novelty-suppressed feeding, social interaction, cfos, activity-mapping

    Received: 06 Jun 2024; Accepted: 27 Aug 2024.

    Copyright: © 2024 Guevara, Alloo, Gupta, Thomas, Del Valle, Magee, Benson and Huntley. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Deanna L. Benson, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, United States
    George W. Huntley, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.