Cell and Tissue Research

, Volume 362, Issue 1, pp 163–176 | Cite as

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

  • Moran Homola
  • Martina Pfeffer
  • Claudia Fischer
  • Herbert Zimmermann
  • Simon C. Robson
  • Horst-Werner KorfEmail author
Regular Article


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.


Adenosine Circadian Ecto-5′-nucleotidase NTPDase1-3 Purinergic signaling 



Anterodorsal thalamic nucleus


Arcuate nucleus


Anteroventral thalamic nucleus


Cornu ammonis

CeC and CeL

Capsular and lateral central amygdala


Medial central amygdala


Cingulate cortex


Choroid plexus


Circadian time


Dentate gyrus


Nucleus of Darkschewitsch


Dorsomedial hypothalamic nucleus




Fasciola cinerea


Globus pallidus


Indusium griseum


Interstitial nucleus of the posterior limb of the anterior commissure


In situ hybridization


Knock out


Lateral habenula


Lateral ventricle


Posterior medial amygdala


Medial habenula


Nucleoside triphosphate diphosphohydrolase


Piriform cortex


Premammillary nucleus dorsal


Premammillary nucleus ventral


Posterior thalamic nuclear group


Hypophysial pars tuberalis


Anterior paraventricular thalamic nucleus


Hypothalamic paraventricular nucleus


Reticular thalamic nucleus


Suprachiasmatic nucleus


Subfornical organ


Stria medullaris


Substantia nigra


Supraoptic nucleus


Subthalamic nucleus


Subventricular zone


Triangular septal nucleus


Third ventricle


Ventromedial hypothalamic nucleus


Ventral posterior thalamic nucleus


Ventral posterior parvicellular thalamic nucleus




Zona incerta



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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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Moran Homola
    • 1
  • Martina Pfeffer
    • 1
  • Claudia Fischer
    • 1
  • Herbert Zimmermann
    • 2
  • Simon C. Robson
    • 3
  • Horst-Werner Korf
    • 1
    Email author
  1. 1.Institute of Anatomy II, Dr. Senckenbergisches Chronomedizinisches Institut (SCI), Goethe UniversityFrankfurt am MainGermany
  2. 2.Institute of Cell Biology and Neuroscience, Molecular and Cellular NeurobiologyGoethe UniversityFrankfurt am MainGermany
  3. 3.Department of Medicine, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA

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