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Role of Astrocytes in Central Respiratory Chemoreception

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Glial Cells in Health and Disease of the CNS

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 949))

Abstract

Astrocytes perform various homeostatic functions in the nervous system beyond that of a supportive or metabolic role for neurons. A growing body of evidence indicates that astrocytes are crucial for central respiratory chemoreception. This review presents a classical overview of respiratory central chemoreception and the new evidence for astrocytes as brainstem sensors in the respiratory response to hypercapnia. We review properties of astrocytes for chemosensory function and for modulation of the respiratory network. We propose that astrocytes not only mediate between CO2/H+ levels and motor responses, but they also allow for two emergent functions: (1) Amplifying the responses of intrinsic chemosensitive neurons through feedforward signaling via gliotransmitters and; (2) Recruiting non-intrinsically chemosensitive cells thanks to volume spreading of signals (calcium waves and gliotransmitters) to regions distant from the CO2/H+ sensitive domains. Thus, astrocytes may both increase the intensity of the neuron responses at the chemosensitive sites and recruit of a greater number of respiratory neurons to participate in the response to hypercapnia.

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Abbreviations

5-HT:

5-hydroxytryptamine (Serotonin)

ACh:

Acetylcholine

aCSF:

Artificial cerebrospinal fluid

AMPAR:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

ANP:

Atrial natriuretic peptide

ATP:

Adenosine triphosphate

CA:

Carbonic anhydrase enzyme

CCHS:

Central congenital hypoventilation syndrome

CNS:

Central nervous system

CNO:

Clozapine-N-oxide

CO2 :

Carbon dioxide

CNQX:

6-cyano-7-nitroquinoxaline-2,3-dione—competitive AMPA/kainate receptor antagonist

cNTS:

Caudal nucleus tractus solitarius

CSF:

Cerebrospinal fluid

cVLM:

Caudal ventrolateral medulla

cVRG:

Caudal ventral respiratory group

Cx:

Connexins

DRC:

Dorsal respiratory columns

EPSP:

Excitatory postsynaptic potentials

GABA:

γ-aminobutyric acid

GFAP:

Glial fibrillary acidic protein

KF:

Pontine Kölliker-Fuse nucleus

KO:

Knock out

LC:

Locus coeruleus

LDT:

Laterodorsal tegmental nucleus

LPBR:

Lateral parabrachial nucleus

LTP:

Long-term potentiation

mRVLM:

Medial portion of the rostral ventrolateral medulla

MS:

Methionine sulfoximine

NK1R:

Neurokinin 1 receptor

NMDA:

N-methyl-D-aspartate

NMDAR:

N-methyl-D-aspartate receptor

NO:

Nitric oxide

NTS:

Nucleus tractus solitarius

PaCO2 :

Partial arterial pressure of carbon dioxide

PCO2 :

Partial pressure of carbon dioxide

PaO2 :

Partial arterial pressure of oxygen

PF-LHA:

Perifornical-lateral hypothalamic area

PNS:

Peripheral nervous system

PPADS:

Pyridoxal-phosphate-6-azophenyl-2=,4=-disulfonate

PPT:

Pedunculopontine tegmental nucleus

preBötC:

PreBötzinger Complex

ORX:

Orexin

ORX-KO:

Prepro-orexin knockout mice

RN:

Medullary raphe nucleus

RPG:

Respiratory pattern generator

RTN/pFRG:

Retrotrapezoid/parafacial respiratory group

RVL:

Nucleus reticularis rostroventrolateralis

RVLM:

Rostral ventrolateral medulla

rVRG:

Rostral ventral respiratory group

SERT:

Serotonin transporter

SIDS:

Sudden infant death syndrome

SP:

Substance P

SSP-SAP:

Saporin–substance P conjugate

TH:

Tyrosine hydroxylase

TIRF:

Total internal reflection fluorescence

TRH:

Thyrotropin releasing hormone

TRP:

Channels Transient receptor potential channels

TS-eEPSCs:

Tractus solitaries-evoked excitatory postsynaptic currents

VLM:

Ventrolateral medullary surface

VMS:

Ventral medullary surface

VRC:

Ventral respiratory columns

VRG:

Ventral respiratory group

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Acknowledgments

Support from Grants Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) #1130874 (JE), Comisión Nacional de Ciencia y Tecnología (CONICYT) #21140669 (MJ Olivares), Comisión Nacional de Ciencia y Tecnología (CONICYT) #21120594 (S Beltrán-Castillo). DICYT-USACH (JE).

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  1. Departamento de Biología, Universidad de Santiago de Chile (USACH), PO 9170022, Santiago, Chile

    Jaime Eugenín León, María José Olivares & Sebastián Beltrán-Castillo

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  1. Jaime Eugenín León
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  2. María José Olivares
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  3. Sebastián Beltrán-Castillo
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Correspondence to Jaime Eugenín León .

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  1. Faculty of Medicine Professor of Neurology, Pontificia Universidad Católica de Chile, Santiago, Chile

    Rommy von Bernhardi

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Eugenín León, J., Olivares, M.J., Beltrán-Castillo, S. (2016). Role of Astrocytes in Central Respiratory Chemoreception. In: von Bernhardi, R. (eds) Glial Cells in Health and Disease of the CNS. Advances in Experimental Medicine and Biology, vol 949. Springer, Cham. https://doi.org/10.1007/978-3-319-40764-7_6

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