FACS Array Profiling Identifies Ecto-5′ Nucleotidase as a Striatopallidal Neuron-Specific Gene Involved in Striatal-Dependent Learning

Ena, Sabrina; Backer, Jean-François De; Schiffmann, Serge N.; d’Exaerde, Alban de Kerchove

doi:10.1523/jneurosci.2989-12.2013

Cited by 44 publications

(40 citation statements)

References 89 publications

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“…Our findings provide an explanation for the lack of the glycoprotein ecto-5′-nucleotidase (NT5e) staining reported earlier in the caudal part of the mouse striatum (Schoen and Graybiel, 1993). Indeed, NT5e, which hydrolyzes adenosine-5′ monophosphate to adenosine (Lee et al, 1986), has been recently found to be selectively expressed in D2R- and A2aR-expressing MSNs [see Table S2 in Heiman et al (2008); Ena et al (2013)].…”

Section: Discussionmentioning

confidence: 99%

“…The MrD exhibits some singular features including densely packed fusiform neurons (Shu et al, 1988) as well as high densities of immunoreactive terminals of a variety of neuropeptides including L-Enkephalin, substance P, neurotensin, somatostatin, cholecystokinin and dynorphin B (Shu et al, 1988, 1990, 1999). Interestingly, the best hallmark distinguishing the MrD from the other parts of the striatum is so far the lack of the striatopallidal-enriched protein, NT5e (Schoen and Graybiel, 1993; Ena et al, 2013). After a careful reviewing of the molecular markers defining the MrD, it is difficult to ascertain that the D2R/A2aR-expressing MSNs-poor zone of the caudal striatum and the MrD are one and the same subdivision.…”

Section: Discussionmentioning

confidence: 99%

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Spatial distribution of D1R- and D2R-expressing medium-sized spiny neurons differs along the rostro-caudal axis of the mouse dorsal striatum

Gangarossa¹,

Espallergues²,

Mailly³

et al. 2013

Front. Neural Circuits

110

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The striatum projection neurons are striatonigral and striatopallidal medium-sized spiny neurons (MSNs) that preferentially express D1 (D1R) and D2 (D2R) dopamine receptors, respectively. It is generally assumed that these neurons are physically intermingled, without cytoarchitectural organization although this has not been tested. To address this question we used BAC transgenic mice expressing enhanced green fluorescence (EGFP) under the control of Drd1a or Drd2 promoter and spatial point pattern statistics. We demonstrate that D1R- and D2R-expressing MSNs are randomly distributed in most of the dorsal striatum, whereas a specific region in the caudal striatum, adjacent to the GPe, lacks neurons expressing markers for indirect pathway neurons. This area comprises almost exclusively D1R-expressing MSNs. These neurons receive excitatory inputs from the primary auditory cortex and the medial geniculate thalamic nucleus and a rich dopamine innervation. This area contains cholinergic and GABAergic interneurons but apparently no D2R/A2aR modulation because no fluorescence was detected in the neuropil of Drd2-EGFP or Drd2-Cre, and Adora-Cre BAC transgenic mice crossed with reporter mice. This striatal area that expresses calbindin D28k, VGluT1 and 2, is poor in μ opiate receptors and preproenkephalin. Altogether, the differences observed in D1R-MSNs, D2R-MSNs, and interneurons densities, as well as the anatomical segregation of D1R- and D2R/A2aR-expressing MSNs suggest that there are regional differences in the organization of the striatum.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Spatial distribution of D1R- and D2R-expressing medium-sized spiny neurons differs along the rostro-caudal axis of the mouse dorsal striatum

Gangarossa¹,

Espallergues²,

Mailly³

et al. 2013

Front. Neural Circuits

110

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“…We analyzed this cerebral region as some evidence points to the existence of striatal hyperdopaminergic activity secondary to hypofunction of the prefrontal dopamine system [32,33], whereas D 2 R and A 2A R are expressed mainly in medium-sized GABAergic spiny neurons [6]. Interestingly, a recent study showed that, in rodent, ecto-5′-nucleotidase is specifically expressed in this neuronal population, being responsible for most of the extracellular adenosine produced in the striatum [34]. Although the distribution of ecto-nucleotidases in the rodent brain has been deeply examined [22], little information was available on humans.…”

Section: Discussionmentioning

confidence: 99%

Reduced striatal ecto-nucleotidase activity in schizophrenia patients supports the “adenosine hypothesis”

Aliagas

Villar-Menéndez

Sévigny

et al. 2013

Purinergic Signalling

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Schizophrenia (SZ) is a major chronic neuropsychiatric disorder characterized by a hyperdopaminergic state. The hypoadenosinergic hypothesis proposes that reduced extracellular adenosine levels contribute to dopamine D 2 receptor hyperactivity. ATP, through the action of ecto-nucleotidases, constitutes a main source of extracellular adenosine. In the present study, we examined the activity of ecto-nucleotidases (NTPDases, ecto-5′-nucleotidase, and alkaline phosphatase) in the postmortem putamen of SZ patients (n=13) compared with aged-matched controls (n=10). We firstly demonstrated, by means of artificial postmortem delay experiments, that ectonucleotidase activity in human brains was stable up to 24 h, indicating the reliability of this tissue for these enzyme determinations. Remarkably, NTPDase-attributable activity (both ATPase and ADPase) was found to be reduced in SZ patients, while ecto-5′-nucleotidase and alkaline phosphatase activity remained unchanged. In the present study, we also describe the localization of these ecto-enzymes in human putamen control samples, showing differential expression in blood vessels, neurons, and glial cells. In conclusion, reduced striatal NTPDase activity may contribute to the pathophysiology of SZ, and it represents a potential mechanism of adenosine signalling impairment in this illness.

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“…; Ena et al . ) and it was shown in lymphocytes that ecto‐5’‐nucleotidase and A 2A R undergo a coordinated induction (Napieralski et al . ).…”

Section: The Role Of A2ar In Neuroprotectionmentioning

confidence: 99%

How does adenosine control neuronal dysfunction and neurodegeneration?

Cunha

2016

Journal of Neurochemistry

378

385

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The adenosine modulation system mostly operates through inhibitory A 1 (A 1 R) and facilitatory A 2A receptors (A 2A R) in the brain. The activity-dependent release of adenosine acts as a brake of excitatory transmission through A 1 R, which are enriched in glutamatergic terminals. Adenosine sharpens salience of information encoding in neuronal circuits: highfrequency stimulation triggers ATP release in the 'activated' synapse, which is locally converted by ecto-nucleotidases into adenosine to selectively activate A 2A R; A 2A R switch off A 1 R and CB1 receptors, bolster glutamate release and NMDA receptors to assist increasing synaptic plasticity in the 'activated' synapse; the parallel engagement of the astrocytic syncytium releases adenosine further inhibiting neighboring synapses, thus sharpening the encoded plastic change. Brain insults trigger a large outflow of adenosine and ATP, as a danger signal. A 1 R are a hurdle for damage initiation, but they desensitize upon prolonged activation. However, if the insult is near-threshold and/or of short-duration, A 1 R trigger preconditioning, which may limit the spread of damage. Brain insults also up-regulate A 2A R, probably to bolster adaptive changes, but this heightens brain damage since A 2A R blockade affords neuroprotection in models of epilepsy, depression, Alzheimer's, or Parkinson's disease. This initially involves a control of synaptotoxicity by neuronal A 2A R, whereas astrocytic and microglia A 2A R might control the spread of damage. The A 2A R signaling mechanisms are largely unknown since A 2A R are pleiotropic, coupling to different G proteins and non-canonical pathways to control the viability of glutamatergic synapses, neuroinflammation, mitochondria function, and cytoskeleton dynamics. Thus, simultaneously bolstering A 1 R preconditioning and preventing excessive A 2A R function might afford maximal neuroprotection. Keywords: A 1 receptor, A 2A receptor, astrocyte, microglia, synaptic plasticity, synaptotoxicity. This article is part of a mini review series: "Synaptic Function and Dysfunction in Brain Diseases". Relevance of modulation systems to tune information flow in brain circuitsThe goal of understanding the flow of information in neuronal circuits has traditionally been centered in studying the key processes sustaining synaptic transmission and plasticity -i.e. the role of glutamate and glutamate receptors, as well as to a lesser extent the role of GABA and its receptors. If one considers an analogy to the experience of watching TV, this corresponds to studying how the ON/OFF button impacts all Received April 4, 2016; revised manuscript received May 23, 2016; accepted June 23, 2016. Address correspondence and reprint requests to R. A. Cunha, Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal. E-mail: cunharod@gmail.com Abbreviations used: A 1 R, adenosine A 1 receptor; A 2A R, adenosine A 2A receptor; ADHD, attention deficit and hyperactivity disorder; BDNF, brain-derived neurotrophi...

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FACS Array Profiling Identifies Ecto-5′ Nucleotidase as a Striatopallidal Neuron-Specific Gene Involved in Striatal-Dependent Learning

Cited by 44 publications

References 89 publications

Spatial distribution of D1R- and D2R-expressing medium-sized spiny neurons differs along the rostro-caudal axis of the mouse dorsal striatum

Spatial distribution of D1R- and D2R-expressing medium-sized spiny neurons differs along the rostro-caudal axis of the mouse dorsal striatum

Reduced striatal ecto-nucleotidase activity in schizophrenia patients supports the “adenosine hypothesis”

How does adenosine control neuronal dysfunction and neurodegeneration?

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