Role of Ectonucleotidases in Synapse Formation During Brain Development: Physiological and Pathological Implications
Author:
Grković Ivana1, Drakulić Dunja1, Martinović Jelena1, Mitrović Nataša1
Affiliation:
1. Department of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, University of Belgrade, Mike Petrovica Alasa 12-14, 11001 Belgrade, Serbia
Abstract
Background:
Extracellular adenine nucleotides and nucleosides, such as ATP and
adenosine, are among the most recently identified and least investigated diffusible signaling factors
that contribute to the structural and functional remodeling of the brain, both during embryonic
and postnatal development. Their levels in the extracellular milieu are tightly controlled by
various ectonucleotidases: ecto-nucleotide pyrophosphatase/phosphodiesterases (E-NPP), alkaline
phosphatases (AP), ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) and ecto-5'-
nucleotidase (eN).
</P><P>
Methods: Studies related to the expression patterns of ectonucleotidases and their known features
during brain development are reviewed, highlighting involvement of these enzymes in synapse
formation and maturation in physiological as well as in pathological states.
</P><P>
Results: During brain development and in adulthood all ectonucleotidases have diverse expression
pattern, cell specific localization and function. NPPs are expressed at early embryonic days, but the
expression of NPP3 is reduced and restricted to ependymal area in adult brain. NTPDase2 is dominant
ectonucleotidase existing in the progenitor cells as well as main astrocytic NTPDase in the
adult brain, while NTPDase3 is fully expressed after third postnatal week, almost exclusively on
varicose fibers. Specific brain AP is functionally associated with synapse formation and this enzyme
is sufficient for adenosine production during neurite growth and peak of synaptogenesis. eN is
transiently associated with synapses during synaptogenesis, however in adult brain it is more glial
than neuronal enzyme.
Conclusion:
Control of extracellular adenine nucleotide levels by ectonucleotidases are important
for understanding the role of purinergic signaling in developing tissues and potential targets in developmental
disorders such as autism.
Funder
Ministry of Education, Science and Technological Development, Republic of Serbia,
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology (medical),Psychiatry and Mental health,Clinical Neurology,Neurology,Pharmacology,General Medicine
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