Prefrontal 5α-Reductase 2 Mediates Male-Specific Acute Stress Response

    January 2025 in “ Science Advances
    Roberto Cadeddu, Giulia Braccagni, Gabriele Floris, Caterina Branca, Eleonora Corridori, Sara Salviati, Pilar Sánchez, Luca Spiro Santovito, Jesús M. Torres, Esperanza Ortega, Graziano Pinna, Philip J. Moos, Simona Scheggi, Marco Bortolato
    TLDR 5α-reductase 2 is crucial for stress response in male rats.
    The study explores the role of the enzyme 5α-reductase 2 (5αR2) in male-specific acute stress responses in rats, revealing that 5αR2 is crucial for synthesizing the neurosteroid allopregnanolone (AP) during stress. Acute stress increased 5αR2 levels in the medial prefrontal cortex of male rats, but not females, indicating a sex-specific mechanism. Knockdown of 5αR2 led to impaired stress responses, such as increased immobility and reduced social interaction, while administering AP restored these responses. The findings suggest that 5αR2 is essential for male stress reactivity and may contribute to sex differences in stress-related psychiatric disorders, highlighting its potential as a therapeutic target.
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