Behavioral assessment and gene expression changes in a mouse model with dysfunctional STAT1 signaling

Behavioral assessment and gene expression changes in a mouse model with dysfunctional STAT1 signaling

Abstract Background Signal transduction via the Signal Transducer and Activator of Transcription 1 (STAT1) pathway is indispensable for mediating the intracellular effects of interferon-α (IFN-α), interferon-γ (IFN-γ) and other cytokines in the brain and, thereby, crucial for antiviral and antibacte...

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Main Authors: Luca Büschgens, Nina Hempel, Aditi Methi, Andre Fischer, Nele Siering, Lars Piepkorn, Olaf Jahn, Thomas Meyer, Oliver Wirths
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Cell Communication and Signaling
Subjects:
STAT signaling
Interferon signaling
Gene expression
Proteome analysis
Behavior
Mice
Online Access:https://doi.org/10.1186/s12964-025-02313-w
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Summary:Abstract Background Signal transduction via the Signal Transducer and Activator of Transcription 1 (STAT1) pathway is indispensable for mediating the intracellular effects of interferon-α (IFN-α), interferon-γ (IFN-γ) and other cytokines in the brain and, thereby, crucial for antiviral and antibacterial responses during potential life-threatening CNS infections. However, the role of STAT1 signaling beyond the known IFN-α and IFN-γ effects in immediate antimicrobial defense is highly context-dependent, and studies in the existing literature using STAT1-targeted mouse models under normal physiological conditions remain scarce. Methods Here, we characterized a STAT1 targeted-disruption mouse model in the absence of infectious stimuli by employing established behavioral testing paradigms and immunohistochemical stainings, as well as bulk hippocampal transcriptomic and proteomic analyses. Results While we found neither overt behavioral alterations nor immunohistochemical changes with respect to microglial phagocytosis or proliferation, significant alterations were detected in gene and protein expression profiles implicated in neuroinflammatory processes and neuroprotection. Conclusion In summary, this study highlights the complex and context-dependent role of STAT1-mediated signaling even in the absence of any detectable behavioral and neuropathological changes.
ISSN:1478-811X

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