Opera Medica et Physiologica

Astrocyte

Differential Contribution of GLAST and GLT-1 to Network Sodium Signaling in the Early Postnatal Hippocampus

Introduction

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Abstract

Recurrent epileptiform activity induces network sodium oscillations in the juvenile hippocampus. In CA1 pyramidal neurons, these oscillations are mainly caused by opening of glutamate-gated ion channels, while in astrocytes, sodium increases are due to sodium-dependent glutamate uptake. Astrocytes express the glutamate transporters GLAST and GLT- 1, which exhibit differential expression patterns during postnatal development. The specific contribution of these transporter subtypes to sodium oscillations is not known. We addressed this question by performing somatic sodium imaging in hippocampal tissue slices from neonatal (postnatal days (P) 2-4) and two-week-old (P14-16) mice. We found that perfusion with Mg2+-free, bicuculline-containing saline caused sodium oscillations in both developmental stages. Moreover, at both P2-4 and P14-16, application of TFB-TBOA to inhibit GLAST and GLT-1 generated fast sodium loading of neurons and termination of oscillatory activity, accompanied by loss of membrane integrity of neurons, while astrocytes experienced only minor increases in baseline sodium. DHK, a GLT-1-specific blocker, induced moderate sodium loading of neurons, reduced the amplitude of neuronal sodium oscillations and increased the oscillation frequency in two-week-old mice. In neonatal animals, DHK increased baseline sodium and reduced the peak amplitude of sodium transients as well, but exerted only moderate effects on network activity. Taken together, our experiments demonstrate the essential role of glutamate uptake for sodium homeostasis and neural function already in the early neonatal brain. Moreover, they suggest that, although GLAST dominates in neonatal tissue and GLT-1 is predominant at P14-16, both transporter subtypes functionally contribute to glutamate clearance during the first three weeks after birth. 

 

Ionic Signalling in Neuronal-Astroglial Interactions

Astroglial excitability

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Abstract

The name astroglia unifies many non-excitable neural cells that act as primary homeostatic cells in the nervous system. Neuronal activity triggers multiple homeostatic responses of astroglia that include increase in metabolic activity and synthesis of neuronal preferred energy substrate lactate, clearance of neurotransmitters and buffering of extracellular K+ ions to name but a few. Many (if not all) of astroglial homeostatic responses are controlled by dynamic changes in the cytoplasmic concentration of two cations, Ca2+ and Na+. Intracellular concentration of these ions is tightly controlled by several transporters and can be rapidly affected by activation of respective fluxes through ionic channels or ion exchangers. Here we provide a comprehensive review of astroglial Ca2+ and Na+ signalling.

Excitation-Energy Coupling and Vesicle-Based Signaling in Astrocytes

Introduction

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Abstract

Most of the human brain mass is occupied by the neocortex, which consists of neurons and non-neurons. The latter cells include astrocytes, a heterogeneous glial cell type. While astrocytes have been considered as neuronsubservient entities for almost a century, it is now becoming evident that they are essential in providing homeostatic support to neural networks and that they also actively participate in information processing in the brain. Astrocytes get excited when neurotransmitters bind to their membrane receptors and feed-back by releasing their own signals. This involves vesicles, which store chemicals termed gliotransmitters or more generally gliosignaling molecules. In the former case chemical messengers get released from astrocytic sites proximal to the synapse, which defines communication to occur in the micro-space of contact between the synapse and the astrocyte. In contrast gliosignaling molecules may also be released into the extracellular space. This mode of release resembles the endocrine system. Hence astrocytes are considered to be part of the gliocrine system in the brain, where the glymphatic system mediates the convection of released molecules. This complex system not only plays a role in cell-to-cell communication but also synchronizes the provision of energy for neural networks. Astrocytes contain glycogen, a form of energy store. Excitation of astrocytes by volume transmitters, such as noradrenaline , released by locus coeruleus neurons, activates adrenergic receptors and stimulates glycogenolysis, providing lactate. This chapter briefly reviews how noradrenaline and astrocytes operate to synchronize excitation and energy provision. Moreover, Ca2+ -dependent fusion of the vesicle membrane with the plasma membrane in astrocytes is discussed.

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