Phosphodiesterase 10A (PDE10A): Regulator of Dopamine Agonist-Induced Gene Expression in the Striatum
Dopamine and other neurotransmitters have the potential to induce neuroplasticity in the striatum via gene regulation. Dopamine receptor-mediated gene regulation relies on second messenger cascades that involve cyclic nucleotides to relay signaling from the synapse to the nucleus. Phosphodiesterases...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/14/2214 |
| _version_ | 1827619099385004032 |
|---|---|
| author | Ryan Bonate Gabriela Kurek Michael Hrabak Santanna Patterson Fernando Padovan-Neto Anthony R. West Heinz Steiner |
| author_facet | Ryan Bonate Gabriela Kurek Michael Hrabak Santanna Patterson Fernando Padovan-Neto Anthony R. West Heinz Steiner |
| author_sort | Ryan Bonate |
| collection | DOAJ |
| description | Dopamine and other neurotransmitters have the potential to induce neuroplasticity in the striatum via gene regulation. Dopamine receptor-mediated gene regulation relies on second messenger cascades that involve cyclic nucleotides to relay signaling from the synapse to the nucleus. Phosphodiesterases (PDEs) catalyze cyclic nucleotides and thus potently control cyclic nucleotide signaling. We investigated the role of the most abundant striatal PDE, PDE10A, in striatal gene regulation by assessing the effects of PDE10A inhibition (by a selective PDE10A inhibitor, TP-10) on gene regulation and by comparing the basal expression of PDE10A mRNA throughout the striatum with gene induction by dopamine agonists in the intact or dopamine-depleted striatum. Our findings show that PDE10A expression is most abundant in the sensorimotor striatum, intermediate in the associative striatum and lower in the limbic striatum. The inhibition of PDE10A produced pronounced increases in gene expression that were directly related to levels of local PDE10A expression. Moreover, the gene expression induced by L-DOPA after dopamine depletion (by 6-OHDA), or by psychostimulants (cocaine, methylphenidate) in the intact striatum, was also positively correlated with the levels of local PDE10A expression. This relationship was found for gene markers of both D1 receptor- and D2 receptor-expressing striatal projection neurons. Collectively, these results indicate that PDE10A, a vital part of the dopamine receptor-associated second messenger machinery, is tightly linked to drug-induced gene regulation in the striatum. PDE10A may thus serve as a potential target for modifying drug-induced gene regulation and related neuroplasticity. |
| first_indexed | 2024-03-09T10:21:29Z |
| format | Article |
| id | doaj.art-a990b2ef14db4390bd3188939212d2dd |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T10:21:29Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-a990b2ef14db4390bd3188939212d2dd2023-12-01T22:00:49ZengMDPI AGCells2073-44092022-07-011114221410.3390/cells11142214Phosphodiesterase 10A (PDE10A): Regulator of Dopamine Agonist-Induced Gene Expression in the StriatumRyan Bonate0Gabriela Kurek1Michael Hrabak2Santanna Patterson3Fernando Padovan-Neto4Anthony R. West5Heinz Steiner6Stanson Toshok Center for Brain Function and Repair, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USAStanson Toshok Center for Brain Function and Repair, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USAStanson Toshok Center for Brain Function and Repair, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USAStanson Toshok Center for Brain Function and Repair, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USADiscipline of Neuroscience, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USADiscipline of Neuroscience, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USAStanson Toshok Center for Brain Function and Repair, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USADopamine and other neurotransmitters have the potential to induce neuroplasticity in the striatum via gene regulation. Dopamine receptor-mediated gene regulation relies on second messenger cascades that involve cyclic nucleotides to relay signaling from the synapse to the nucleus. Phosphodiesterases (PDEs) catalyze cyclic nucleotides and thus potently control cyclic nucleotide signaling. We investigated the role of the most abundant striatal PDE, PDE10A, in striatal gene regulation by assessing the effects of PDE10A inhibition (by a selective PDE10A inhibitor, TP-10) on gene regulation and by comparing the basal expression of PDE10A mRNA throughout the striatum with gene induction by dopamine agonists in the intact or dopamine-depleted striatum. Our findings show that PDE10A expression is most abundant in the sensorimotor striatum, intermediate in the associative striatum and lower in the limbic striatum. The inhibition of PDE10A produced pronounced increases in gene expression that were directly related to levels of local PDE10A expression. Moreover, the gene expression induced by L-DOPA after dopamine depletion (by 6-OHDA), or by psychostimulants (cocaine, methylphenidate) in the intact striatum, was also positively correlated with the levels of local PDE10A expression. This relationship was found for gene markers of both D1 receptor- and D2 receptor-expressing striatal projection neurons. Collectively, these results indicate that PDE10A, a vital part of the dopamine receptor-associated second messenger machinery, is tightly linked to drug-induced gene regulation in the striatum. PDE10A may thus serve as a potential target for modifying drug-induced gene regulation and related neuroplasticity.https://www.mdpi.com/2073-4409/11/14/2214dopamineL-DOPAcocainestriatumphosphodiesterasecyclic nucleotide |
| spellingShingle | Ryan Bonate Gabriela Kurek Michael Hrabak Santanna Patterson Fernando Padovan-Neto Anthony R. West Heinz Steiner Phosphodiesterase 10A (PDE10A): Regulator of Dopamine Agonist-Induced Gene Expression in the Striatum Cells dopamine L-DOPA cocaine striatum phosphodiesterase cyclic nucleotide |
| title | Phosphodiesterase 10A (PDE10A): Regulator of Dopamine Agonist-Induced Gene Expression in the Striatum |
| title_full | Phosphodiesterase 10A (PDE10A): Regulator of Dopamine Agonist-Induced Gene Expression in the Striatum |
| title_fullStr | Phosphodiesterase 10A (PDE10A): Regulator of Dopamine Agonist-Induced Gene Expression in the Striatum |
| title_full_unstemmed | Phosphodiesterase 10A (PDE10A): Regulator of Dopamine Agonist-Induced Gene Expression in the Striatum |
| title_short | Phosphodiesterase 10A (PDE10A): Regulator of Dopamine Agonist-Induced Gene Expression in the Striatum |
| title_sort | phosphodiesterase 10a pde10a regulator of dopamine agonist induced gene expression in the striatum |
| topic | dopamine L-DOPA cocaine striatum phosphodiesterase cyclic nucleotide |
| url | https://www.mdpi.com/2073-4409/11/14/2214 |
| work_keys_str_mv | AT ryanbonate phosphodiesterase10apde10aregulatorofdopamineagonistinducedgeneexpressioninthestriatum AT gabrielakurek phosphodiesterase10apde10aregulatorofdopamineagonistinducedgeneexpressioninthestriatum AT michaelhrabak phosphodiesterase10apde10aregulatorofdopamineagonistinducedgeneexpressioninthestriatum AT santannapatterson phosphodiesterase10apde10aregulatorofdopamineagonistinducedgeneexpressioninthestriatum AT fernandopadovanneto phosphodiesterase10apde10aregulatorofdopamineagonistinducedgeneexpressioninthestriatum AT anthonyrwest phosphodiesterase10apde10aregulatorofdopamineagonistinducedgeneexpressioninthestriatum AT heinzsteiner phosphodiesterase10apde10aregulatorofdopamineagonistinducedgeneexpressioninthestriatum |