CD73 Is a Major Regulator of Adenosinergic Signalling in Mouse Brain

Abstract

CD73 (ecto-5’-nucleotidase) is a cell surface enzyme that regulates purinergic signalling by desphosphorylating extracellular AMP to adenosine. 5′-nucleotidases are known to be expressed in brain, but the expression of CD73 and its putative physiological functions at this location remain elusive. Here we found, using immunohistochemistry of wild-type and CD73 deficient mice, that CD73 is prominently expressed in the basal ganglia core comprised of striatum (caudate nucleus and putamen) and globus pallidus. Furthermore, meninges and the olfactory tubercle were found to specifically express CD73. Analysis of wild type (wt) and CD73 deficient mice revealed that CD73 confers the majority of 5’-nucleotidase activity in several areas of the brain. In a battery of behavioural tests and in IntelliCage studies, the CD73 deficient mice demonstrated significantly enhanced exploratory locomotor activity, which probably reflects the prominent expression of CD73 in striatum and globus pallidus that are known to control locomotion. Furthermore, the CD73 deficient mice displayed altered social behaviour. Overall, our data provide a novel mechanistic insight into adenosinergic signalling in brain, which is implicated in the regulation of normal and pathological behaviour.

AMIGO-Kv2.1 Potassium Channel Complex is Associated With Schizophrenia-Related Phenotypes

“…The behavioral tests were carried out as described previously 31,32 with the exception of beam walking test, and adaptation to drinking session and patrolling in IntelliCage. The detailed description of individual behavioral tests and protocols applied in IntelliCage is included in the supplementary material.…”

Vascular and extravascular distribution of the ATP-binding cassette transporters ABCB1 and ABCC1 in aged human brain and pituitary

“…To learn more about a possible connection between neuronal localization of both transporter proteins and this particular type of neuromodulation, we compared the distribution of ABCB1 and ABCC1 with those of 5-N´ ADA and NTPDase2. Since all three enzymes are important regulators of purinergic cell signalling (Burnstock, 2013; Gampe et al, 2012; Kulesskaya et al, 2013; Mutafova-Yambolieva and Durnin, 2014) by degrading ATP (5-N´ degrades 5´-AMP to adenosine, ADA degrades adenosine to inosine and NTPDase2 hydrolyses extracellular nucleoside triphosphates to nucleoside monophosphates) they have repeatedly been used as putative marker enzymes to anatomically localize adenosinergic/purinergic neuromodulation (Bernstein et al, 1978; Kulesskaya et al, 2013; Staines et al, 1988; Yamamoto et al, 1987)). However, due to their wide distribution within the brain ((Burnstock et al, 2011); this study) the immunodetection of 5´-N and/or ADA in a specific brain cell compartment does not unequivocally prove the presence of purinergic/adenosinergic neuromodulation).…”

The Adenosinergic System

“…In the odor detection and processing, ATP has been well characterized as a mediator of odor sensitivity and information processing in taste buds (Finger et al 2005;Hegg et al 2003;Kinnamon and Finger 2013), whereas a role for adenosine receptors has been ascribed to sweet buds in particular (Dando et al 2012;Kataoka et al 2012) and in the control of astrocytes (Doengi et al 2008). The interferon-inducible RNAspecific adenosine deaminase (ADA) is an RNA editing enzyme implicated in the site-selective deamination of adenosine to inosine in cellular pre-mRNAs (Liu et al 1999;Senba et al 1987) and CD73 (ecto-5′-nucleotidase) is a cell surface enzyme that regulates purinergic signaling by dephosphorylating extracellular AMP to adenosine (Kulesskaya et al 2013) and both display an high expression and activity in the olfactory bulb (Kulesskaya et al 2013;Liu et al 1999;Senba et al 1987). Thus, A 1 R and A 2A R mRNA is highly expressed in the granule cell layer of adult and developing olfactory bulb of rodents (Kaelin-Lang et al 1999).…”