Brain metabolic sensing and metabolic signaling at the level of an astrocyte.

Nephtali Marina,Shahriar Sheikhbahaei,Egor Turovsky,Patrick S Hosford,Richard Ang,Svetlana Mastitskaya,Alexander V Gourine,Alla Korsak,Isabel N Christie,Shefeeq M Theparambil,Anna Hadjihambi

doi:10.1002/glia.23283

Nephtali Marina, Shahriar Sheikhbahaei + Show 9 more

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https://doi.org/10.1002/glia.23283

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Journal: Glia	Publication Date: Dec 23, 2017
Citations: 89	License type: CC BY 4.0

Affiliation: University College London, Institute of Cell Biophysics

Abstract

Astrocytes support neuronal function by providing essential structural and nutritional support, neurotransmitter trafficking and recycling and may also contribute to brain information processing. In this article we review published results and report new data suggesting that astrocytes function as versatile metabolic sensors of central nervous system (CNS) milieu and play an important role in the maintenance of brain metabolic homeostasis. We discuss anatomical and functional features of astrocytes that allow them to detect and respond to changes in the brain parenchymal levels of metabolic substrates (oxygen and glucose), and metabolic waste products (carbon dioxide). We report data suggesting that astrocytes are also sensitive to circulating endocrine signals—hormones like ghrelin, glucagon‐like peptide‐1 and leptin, that have a major impact on the CNS mechanisms controlling food intake and energy balance. We discuss signaling mechanisms that mediate communication between astrocytes and neurons and consider how these mechanisms are recruited by astrocytes activated in response to various metabolic challenges. We review experimental data suggesting that astrocytes modulate the activities of the respiratory and autonomic neuronal networks that ensure adaptive changes in breathing and sympathetic drive in order to support the physiological and behavioral demands of the organism in ever‐changing environmental conditions. Finally, we discuss evidence suggesting that altered astroglial function may contribute to the pathogenesis of disparate neurological, respiratory and cardiovascular disorders such as Rett syndrome and systemic arterial hypertension.

Highlights

The central nervous system (CNS) plays a key role in the maintenance of energy homeostasis
In global methyl-CpG-binding protein 2 (MeCP2) gene knockout mice, selective re-expression of MeCP2 in astrocytes rescues the normal respiratory pattern (Lioy et al, 2011). These data indicate that the brainstem networks of the respiratory neurons, including chemosensitive retrotrapezoid nucleus (RTN) neurons, are not able to mount an appropriate ventilatory response to CO2 when astroglial function and pH-sensitivity are compromised, supporting the idea of a critical role played by astroglial pH-sensitivity in the CNS mechanisms which transmit changes in brain parenchymal pressure of CO2 (PCO2)/pH into a modified pattern of breathing
There is evidence that the central effects of GLP-1 analogs are associated with excitation of pre-sympathetic C1 neurons, increases in central sympathetic drive, systemic arterial blood pressure and heart rate (Yamamoto et al, 2002). These effects are likely to be attributed to direct activation of neuronal GLP-1 receptors (GLP-1R), the data reported and discussed above suggest that brainstem astrocytes may contribute to GLP-1-induced sympathoexcitation via Ca21-dependent release of signaling molecules that activate pre-sympathetic circuits (e.g., adenosine triphosphate (ATP))

Summary

Introduction

The central nervous system (CNS) plays a key role in the maintenance of energy homeostasis. It was reported that [Ca21]i responses in astrocytes induced by optogenetic stimulation lead to excitation of neighboring C1 neurons in the brainstem slices in vitro and trigger increases in renal sympathetic nerve activity, heart rate and the systemic arterial blood pressure in anesthetized rats in vivo (Marina et al, 2013).

Results

Conclusion