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Expression of ectonucleotidases in the prosencephalon of melatonin-proficient C3H and melatonin-deficient C57Bl mice: spatial distribution and time-dependent changes

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Abstract

Extracellular purines (ATP, ADP, AMP and adenosine) are important signaling molecules in the CNS. Levels of extracellular purines are regulated by enzymes located at the cell surface referred to as ectonucleotidases. Time-dependent changes in their expression could profoundly influence the availability of extracellular purines and thereby purinergic signaling. Using radioactive in situ hybridization, we analyzed the mRNA distribution of the enzymes NTPDase1, -2 and -3 and ecto-5′-nucleotidase in the prosencephalon of two mouse strains: melatonin-proficient C3H and melatonin-deficient C57Bl. The mRNAs of these enzymes were localized to specific brain regions, such as hippocampus, striatum, medial habenula and ventromedial hypothalamus. NTPDase3 expression was more widely distributed than previously thought. All ectonucleotidases investigated revealed a prominent time-dependent expression pattern. In C3H, the mRNA expression of all four enzymes gradually increased during the day and peaked during the night. In contrast, in C57Bl, ecto-5′-nucleotidase expression peaked at the beginning of the day and gradually decreased to trough levels at night. Recording of locomotor activity revealed higher daytime activity of C57Bl than of C3H. Our results indicate that the expression of ectonucleotidases varies according to time and genotype and suggest that melatonin exerts modulatory effects associated with different regulations of purinergic signaling in the brain. These findings provide an important basis for further examination of the complexity of the purinergic system in the brain.

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Abbreviations

AD:

Anterodorsal thalamic nucleus

Arc:

Arcuate nucleus

AV:

Anteroventral thalamic nucleus

CA:

Cornu ammonis

CeC and CeL:

Capsular and lateral central amygdala

CeM:

Medial central amygdala

Cg:

Cingulate cortex

CP:

Choroid plexus

CT:

Circadian time

DG:

Dentate gyrus

Dk:

Nucleus of Darkschewitsch

DM:

Dorsomedial hypothalamic nucleus

eN:

Ecto-5′-nucleotidase

FC:

Fasciola cinerea

GP:

Globus pallidus

IG:

Indusium griseum

IPAC:

Interstitial nucleus of the posterior limb of the anterior commissure

ISH:

In situ hybridization

KO:

Knock out

LHb:

Lateral habenula

LV:

Lateral ventricle

MeP:

Posterior medial amygdala

MHb:

Medial habenula

NTPDase:

Nucleoside triphosphate diphosphohydrolase

Pir:

Piriform cortex

PMD:

Premammillary nucleus dorsal

PMV:

Premammillary nucleus ventral

Po:

Posterior thalamic nuclear group

PT:

Hypophysial pars tuberalis

PVA:

Anterior paraventricular thalamic nucleus

PVN:

Hypothalamic paraventricular nucleus

Rt:

Reticular thalamic nucleus

SCN:

Suprachiasmatic nucleus

SFO:

Subfornical organ

sm:

Stria medullaris

SN:

Substantia nigra

SON:

Supraoptic nucleus

STh:

Subthalamic nucleus

SVZ:

Subventricular zone

TS:

Triangular septal nucleus

3V:

Third ventricle

VMH:

Ventromedial hypothalamic nucleus

VP:

Ventral posterior thalamic nucleus

VPPC:

Ventral posterior parvicellular thalamic nucleus

WT:

Wild-type

ZI:

Zona incerta

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Acknowledgments

This work has been supported by the Dr. Senckenbergische Stiftung, Frankfurt am Main. We would like to thank Dr. Hanns Ackermann (Institute for Biostatistics und Mathematic Modelling, Goethe University, Frankfurt am Main, Germany) for his kind help with the statistical analyses.

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Authors and Affiliations

  1. Institute of Anatomy II, Dr. Senckenbergisches Chronomedizinisches Institut (SCI), Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany

    Moran Homola, Martina Pfeffer, Claudia Fischer & Horst-Werner Korf

  2. Institute of Cell Biology and Neuroscience, Molecular and Cellular Neurobiology, Goethe University, Max-von-Laue-Str. 13, 60438, Frankfurt am Main, Germany

    Herbert Zimmermann

  3. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 3 Blackfan Circle, Boston, MA, 02215, USA

    Simon C. Robson

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  1. Moran Homola
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Correspondence to Horst-Werner Korf.

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Homola, M., Pfeffer, M., Fischer, C. et al. Expression of ectonucleotidases in the prosencephalon of melatonin-proficient C3H and melatonin-deficient C57Bl mice: spatial distribution and time-dependent changes. Cell Tissue Res 362, 163–176 (2015). https://doi.org/10.1007/s00441-015-2179-7

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