Minocycline alters expression of inflammatory markers in autonomic brain areas and ventilatory responses induced by acute hypoxia

New Findings

• What is the central question of this study?

  Microglia are presumably the source of inflammatory mediators, which contribute to hypoxia-induced neuroinflammation. However, the relationship between microglia activity during hypoxia and inflammatory responses in specific autonomic brain regions is not well understood. Therefore, we hypothesize that acute hypoxia (AH) initiates an immune response in the central nervous system elicited by an increased expression of inflammatory mediators in specific brain areas related to autonomic control.

• What is the main finding and its importance?

  Acute hypoxia initiated neuroinflammatory mechanisms specifically in brain autonomic nuclei responsible for cardiorespiratory control, i.e the RVLM and PVH. Our findings emphasize the importance of microglia for the maintenance of autonomic adjustments during physiological challenges, such as hypoxia, or during cardiorespiratory reflex activation elicited by the arterial chemoreceptors.

Abstract

Prolonged and continuous exposure of mammals to a low oxygen environment (chronic hypoxia) elicits remarkable morphological and physiological adjustments. These include altered gene expression, increased peripheral chemosensitivity, enhanced respiratory drive and sympathoexcitation. The current study examines the hypothesis that acute hypoxia (AH) initiates an immune response in the central nervous system elicited by an increased expression of inflammatory mediators in specific brain areas related to autonomic control. Male Wistar rats pretreated with vehicle or minocycline (30 mg/kg/day for 5 days) were subjected to AH (8% O₂, balanced with N₂) or normoxia (21% O₂) for 3 hours. AH increased IL-6, IL-1β and MMP9 mRNA expression in the PVH and RVLM and TNFα in the RVLM. Treatment with minocycline, an inhibitor of microglial activation, decreased IL-1β, TNFα and MMP9 mRNA expression in the RVLM, and increased IL-6 mRNA expression in the RVLM and PVH of rats exposed to AH. Minocycline treatment also elicited a decrease in the number of activated neurons in the RVLM/C1 neurons (expressed as Fos⁺/TH⁺), the number of Fos-activated neurons in the PVH and the increase in ventilation elicited by AH. When viewed together, these results suggest that AH modulates the expression of inflammatory mediators in autonomic brain nuclei that may be involved in the responses to chemoreceptor activation.

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