From stress to anhedonia: differential gene expression, behavioural and biochemical modulations in resilient versus susceptible mice in an ultrasound model of juvenile depression

Strekalova T. de Munter J. Gorlova A. Cespuglio R. Deykin A.V. Lyundup A. Burova A. Kochina E. Sitdikova K. Umriukhin A. Shulgin B. Grünblatt E. Walitza S.
September 2025 Springer

Journal of Neural Transmission
2025 #132 Issue 9 1313 - 1333 pp.

Juvenile depression is an increasingly recognized mental health condition, distinct from adult depression. ‘Emotional stress’, i.e., adverse experience of primarily psychological nature, is a risk factor of particular importance for juvenile depression. Like adults, adolescents display variable susceptibility to depression precipitated by stress, the nature of which is poorly understood. We employed the 3-week ultrasound (US) stress in juvenile C57BL/6 mice to compare behavioral and molecular features of susceptible and resilient to depressive-like syndrome subsets of animals. Mice were exposed to alternating frequencies of 20–25 kHz and 25–45 kHz, an established model of ‘emotional stress’. In the sucrose test, mice were categorized as anhedonic (stress-susceptible) or non-anhedonic (stress-resilient), upon their sucrose preference that decreased below control values in some but not all animals. Parameters of emotionality, social and locomotor behaviors, learning, serum corticosterone levels, brain gene expression of pro-inflammatory cytokines, and malondialdehyde (MDA) concentrations were studied. In comparison with controls, susceptible mice exhibited prolonged floating behavior in the swim test, increased anxiety-like and dominant-type social behaviors, elevated corticosterone plasma levels, increased brain expression of cytokines interleukin-1 β (Il-1β) and tumor necrosis factor (Tnf), reduced expression of proteolipid protein 1 (Plp1) and myelin-associated glycoprotein (Mag). These changes were not found in resilient mice. Brain MDA concentrations similarly increased in both groups. Hence, the ultrasound stress model appears to replicate several behavioral features relevant to juvenile depression in mice, suggesting its potential as a tool for investigating various aspects of adolescent depression. Additionally, it introduces the stratification of animals into ‘resilient’ and ‘susceptible’ subgroups, which may contribute to a better understanding of the mechanisms associated with stress resilience during adolescence.

Emotionality , Juvenile depression , Mice , Pro-inflammatory cytokines , Resilience , Ultrasound stress

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Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 40, ER Maastricht 6229, Maastricht, Netherlands
Present address: Neuroplast BV, Maastricht, Netherlands
Research and Education Resource Center, Peoples Friendship University of Russia (RUDN University), Moscow, Russian Federation
Neuroscience Research Center of Lyon, Claude-Bernard Lyon-1 University, Bron, France
Laboratory of Genetic Technology and Gene Editing for Biomedicine and Veterinary, National Research Belgorod state University, Belgorod, Russian Federation
Department of Normal Physiology, Sechenov Moscow State Medical University, Moscow, Russian Federation
Center for Life Sciences, National Astana Laboratory, Nazarbayev State University, Astana, Kazakhstan
Department Laboratory of Engineering Profile Physical and Chemical Methods of Analysis, Korkyt Ata Kyzylorda University, Kyzylorda, Kazakhstan
Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland
Neuroscience Center Zurich, University of Zurich and the ETH Zurich, Zurich, Switzerland
Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland

Department of Psychiatry and Neuropsychology
Present address: Neuroplast BV
Research and Education Resource Center
Neuroscience Research Center of Lyon
Laboratory of Genetic Technology and Gene Editing for Biomedicine and Veterinary
Department of Normal Physiology
Center for Life Sciences
Department Laboratory of Engineering Profile Physical and Chemical Methods of Analysis
Department of Child and Adolescent Psychiatry and Psychotherapy
Neuroscience Center Zurich
Zurich Center for Integrative Human Physiology

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