Minocycline attenuates panicogenic responses in a CO2-induced panic attack model: a translational approach

Le résumé fourni par la source

There is a connection between neuroinflammation and panic attacks (PA), as microglia-driven pro-inflammatory responses help detect homeostatic disturbances like CO₂ inhalation. This model has become widely used in research since CO₂ exposure can trigger PA in humans and panic-related behavior in mice. Minocycline inhibits microglia activation, serving as a promising tool to attenuate CO2-induced PA. The locus coeruleus (LC) is a CO₂/pH-sensitive region, and disruptions in its activity are linked to psychiatric conditions such as panic disorder (PD). We investigated the involvement of microglia in the respiratory and behavioral responses induced by CO2 in mice and the effect of minocycline and clonazepam treatment. We also assessed in mice whether LC microglia are activated after hypercapnia using IBA-1 immunohistochemistry. Translationally, PD patients were treated with minocycline and clonazepam and examined for their CO2-responsiveness. LC microglia were activated 6 h after exposure to 20% CO2 in mice. This panicogenic stimulus also induced hyperventilation as well as active panic-related escape responses, characterized by jumps and running episodes. Minocycline and clonazepam decreased escape expression during the CO2 challenge, but only the former drug reduced hyperventilatory responses. None of the drugs changed IL levels in LC. In humans, minocycline reduced the severity of CO2-induced panic attacks and also modulated the immune response by lowering IL-2sRα and increasing IL-10 levels. Exposure to hypercapnia activates microglia in the LC of mice. Treatment with minocycline, similar to the clinically effective panicolytic clonazepam, attenuates CO2-induced panic-like responses in both mice and humans. These results support the potential of minocycline as a therapeutic strategy for PD.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.