Pivotal role of phosphodiesterase 10A in the integration of dopamine signals in mice striatal D<sub>1</sub> and D<sub>2</sub> medium‐sized spiny neurones

Mota, Élia; Bompierre, Ségolène; Betolngar, Dahdjim; Castro, Liliana; Vincent, Pierre

doi:10.1111/bph.15664

Cited by 6 publications

(3 citation statements)

References 63 publications

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“…In our experiments, we observed little or no signs of PDE2A or PDE10A activity in ChINs, consistent with the documented absence of their mRNA in these cells (22,33,34). This stands in contrast with the important functional role played by PDE2A and PDE10A in MSNs (36,46,50).…”

Section: Phosphodiesterases In Chinssupporting

confidence: 88%

“…In our experiments, we observed no signs of PDE2A or PDE10A activity in ChINs, consistent with the documented absence of their mRNA in these cells (Saunders et al ., 2018; Xie et al ., 2006; Sano et al ., 2008). This stands in contrast with the important functional role played by PDE2A and PDE10A in MSNs (Polito et al ., 2013; Polito et al ., 2015; Mota et al ., 2021a).…”

Section: Discussionmentioning

confidence: 99%

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Cross-pathway integration of cAMP signals through cGMP and calcium-regulated phosphodiesterases in mouse striatal cholinergic interneurons

Bompierre,

Byelyayeva,

Mota

et al. 2023

Preprint

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Acetylcholine plays a key role in striatal function, yet the intricate dynamics of cyclic nucleotide signaling which govern the firing properties of cholinergic interneurons (ChINs) have remained elusive. Since phosphodiesterases determine the dynamics of cyclic nucleotides, in this study, we used FRET biosensors and pharmacological compounds to examine phosphodiesterase activity in ChINs in mouse brain slices. Intriguingly, these neurons displayed strikingly low levels and slow cAMP responsiveness compared to medium-sized spiny neurons (MSNs). Our experiments revealed that PDE1, PDE3 and PDE4 are important regulators of cAMP level in ChINs. Notably, the induction of cGMP production by nitric oxide (NO) donors increases cAMP by inhibiting PDE3 - a mechanism hitherto unexplored in neuronal context. Furthermore, the activation of NMDA or metabotropic glutamate receptors increases intracellular calcium, consequently activating PDE1 and thereby decreasing both cAMP and cGMP. This interplay of phosphodiesterases enables the control of cAMP by the neuromodulatory influences of glutamate and NO. Remarkably, the NO/cGMP signal results in different effects: NO enhances cAMP in ChINs by inhibiting PDE3, whereas it reduces cAMP levels in MSNs by activating PDE2A. These findings underscore the specificity of intracellular signaling in ChINs compared to MSNs and show how the NO-cGMP pathway affects these various neuronal types differently. These observations have significant implications for understanding the regulation of the striatal network and the integration of dopaminergic signals and suggest innovative therapeutic strategies for addressing basal ganglia disorders with unmet medical need.

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Section: Phosphodiesterases In Chinssupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Cross-pathway integration of cAMP signals through cGMP and calcium-regulated phosphodiesterases in mouse striatal cholinergic interneurons

Bompierre,

Byelyayeva,

Mota

et al. 2023

Preprint

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“…cAMP is the second messenger, which plays a major role in cytokine secretion and cell signal transduction [ 29 , 30 ]. In cells, the expression of cAMP is regulated by adenosine A2A receptor (A2AR) and PDE10A [ 31 , 32 ]. The inhibition of PDE10A leads to increased intracellular cAMP levels and activates the PKA signaling pathway [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of PDE10A-Rescued TBI-Induced Neuroinflammation and Apoptosis through the cAMP/PKA/NLRP3 Pathway

Huang

Dang

Cao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Phosphodiesterase 10A (PDE10A) is a dual-substrate phosphodiesterase that is highly expressed in the striatal complex. PDE10A is an important target for the treatment of ganglion dysfunction and neuroinflammation-related diseases, but its possible impact on traumatic brain injury (TBI) is still unclear. This study aims to investigate the protective effects of inhibiting PDE10A on neuroinflammation post-TBI injury and its possible molecular mechanism. The expression of PDE10A in rats and HT22 cells was determined by Western blotting. The neurological dysfunction of these rats was detected by Nissl staining, hematoxylin-eosin (HE) staining, and Morris water maze test. The activity of HT22 cells was measured by MTT. The findings of this study suggest that PDE10A is highly expressed in the brain tissue of TBI rats and HT22 cells induced by mechanical injury. Inhibition of PDE10A reduces the expression of interleukin-1β (IL-1β) and interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in HT22 cells induced by mechanical injury to inhibit cell apoptosis. Simultaneously, inhibition of PDE10A in TBI rats reduces the time to find a visible platform in the same pool, while cAMP/PKA activator treatment alleviates all of the abovementioned phenomena. Additionally, it is further confirmed that inhibition of PDE10A activates the cAMP/PKA pathway and downregulates the expression of NRLP3. These findings demonstrate that inhibition of PDE10A exerts neuroprotection by inhibiting apoptosis and inflammation following TBI, at least partially by the cAMP/PKA/NLRP3 pathway.

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Polyoxometalate-cyclodextrin supramolecular entities for real-time in situ monitoring of dopamine released from neuroblastoma cells

Shetty

Moosa

Zhang

et al. 2023

Biosensors and Bioelectronics

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Pivotal role of phosphodiesterase 10A in the integration of dopamine signals in mice striatal D₁ and D₂ medium‐sized spiny neurones

Cited by 6 publications

References 63 publications

Cross-pathway integration of cAMP signals through cGMP and calcium-regulated phosphodiesterases in mouse striatal cholinergic interneurons

Cross-pathway integration of cAMP signals through cGMP and calcium-regulated phosphodiesterases in mouse striatal cholinergic interneurons

Inhibition of PDE10A-Rescued TBI-Induced Neuroinflammation and Apoptosis through the cAMP/PKA/NLRP3 Pathway

Polyoxometalate-cyclodextrin supramolecular entities for real-time in situ monitoring of dopamine released from neuroblastoma cells

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Pivotal role of phosphodiesterase 10A in the integration of dopamine signals in mice striatal D1 and D2 medium‐sized spiny neurones

Cited by 6 publications

References 63 publications

Cross-pathway integration of cAMP signals through cGMP and calcium-regulated phosphodiesterases in mouse striatal cholinergic interneurons

Cross-pathway integration of cAMP signals through cGMP and calcium-regulated phosphodiesterases in mouse striatal cholinergic interneurons

Inhibition of PDE10A-Rescued TBI-Induced Neuroinflammation and Apoptosis through the cAMP/PKA/NLRP3 Pathway

Polyoxometalate-cyclodextrin supramolecular entities for real-time in situ monitoring of dopamine released from neuroblastoma cells

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Resources

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Pivotal role of phosphodiesterase 10A in the integration of dopamine signals in mice striatal D₁ and D₂ medium‐sized spiny neurones