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Publication Detail
Astrocytes modulate baroreflex sensitivity at the level of the nucleus of the solitary tract
  • Publication Type:
    Journal article
  • Publication Sub Type:
  • Authors:
    Mastitskaya S, Turovsky E, Marina N, Theparambil SM, Hadjihambi A, Kasparov S, Teschemacher AG, Ramage AG, Gourine AV, Hosford PS
  • Publication date:
  • Journal:
    Journal of Neuroscience
  • Status:
    Published online
  • Country:
    United States
  • PII:
  • Language:
Maintenance of cardiorespiratory homeostasis depends on autonomic reflexes controlled by neuronal circuits of the brainstem. The neurophysiology and neuroanatomy of these reflex pathways are well understood, however, the mechanisms and functional significance of autonomic circuit modulation by glial cells remain largely unknown. In experiments conducted in male laboratory rats we show that astrocytes of the nucleus tractus solitarii (NTS), the brain area that receives and integrates sensory information from the heart and blood vessels, respond to incoming afferent inputs with [Ca2+]i elevations. Astroglial [Ca2+]i responses are triggered by transmitters released by vagal afferents, glutamate acting at AMPA receptors and 5-HT acting at 5-HT2A receptors. In conscious freely behaving animals blockade of Ca2+-dependent vesicular mechanisms in NTS astrocytes by virally driven expression of a dominant-negative SNARE protein (dnSNARE) increased baroreflex sensitivity by 70% (p<0.001). The effect of compromised astroglial function was specific to the NTS as expression of dnSNARE in astrocytes of the ventrolateral brainstem had no effect. ATP considered the principle gliotransmitter and is released by vesicular mechanisms affected by dnSNARE expression. Consistent with this hypothesis, in anesthetized rats, activation P2Y1 purinoceptors in the NTS decreased baroreflex gain by 40% (p=0.031), while blockade of P2Y1 receptors increased baroreflex gain by 57% (p=0.018). These results suggest that glutamate and 5-HT released by NTS afferent terminals trigger Ca2+-dependent astroglial release of ATP to modulate baroreflex sensitivity via P2Y1 receptors. These data add to the growing body of evidence supporting an active role of astrocytes in the brain information processing.SIGNIFICANCE STATEMENTCardiorespiratory reflexes maintain autonomic balance and ensure cardiovascular health. Impaired baroreflex may contribute to the development of cardiovascular disease and serves as a robust predictor of cardiovascular and all-cause mortality. The data obtained in this study suggest that astrocytes are integral components of the brainstem mechanisms that process afferent information and modulate baroreflex sensitivity via the release of ATP. Any condition associated with higher levels of 'ambient' ATP in the NTS would be expected to decrease baroreflex gain by the mechanism described here. As ATP is the primary signalling molecule of glial cells (astrocytes, microglia) responding to metabolic stress and inflammatory stimuli, our study suggests a plausible mechanism of how the central component of baroreflex is affected in pathological conditions.
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