Lack or inhibition of dopaminergic stimulation induces a development increase of striatal tyrosine hydroxylase-positive interneurons.
We examined the role of endogenous dopamine (DA) in regulating the number of intrinsic tyrosine hydroxylase-positive (TH(+)) striatal neurons using mice at postnatal day (PND) 4 to 8, a period that corresponds to the developmental peak in the number of these neurons. We adopted the strategy of deple...
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2012
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oai:doaj.org-article:6da1b2f0862e41f485d504302ead7c112021-11-18T07:05:19ZLack or inhibition of dopaminergic stimulation induces a development increase of striatal tyrosine hydroxylase-positive interneurons.1932-620310.1371/journal.pone.0044025https://doaj.org/article/6da1b2f0862e41f485d504302ead7c112012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028485/?tool=EBIhttps://doaj.org/toc/1932-6203We examined the role of endogenous dopamine (DA) in regulating the number of intrinsic tyrosine hydroxylase-positive (TH(+)) striatal neurons using mice at postnatal day (PND) 4 to 8, a period that corresponds to the developmental peak in the number of these neurons. We adopted the strategy of depleting endogenous DA by a 2-day treatment with α-methyl-p-tyrosine (αMpT, 150 mg/kg, i.p.). This treatment markedly increased the number of striatal TH(+) neurons, assessed by stereological counting, and the increase was highly correlated to the extent of DA loss. Interestingly, TH(+) neurons were found closer to the clusters of DA fibers after DA depletion, indicating that the concentration gradient of extracellular DA critically regulates the distribution of striatal TH(+) neurons. A single i.p. injection of the D1 receptor antagonist, SCH23390 (0.1 mg/kg), the D2/D3 receptor antagonist, raclopride (0.1 mg/kg), or the D4 receptor antagonist, L-745,870 (5 mg/kg) in mice at PND4 also increased the number of TH(+) neurons after 4 days. Treatment with the D1-like receptor agonist SKF38393 (10 mg/kg) or with the D2-like receptor agonist, quinpirole (1 mg/kg) did not change the number of TH(+) neurons. At least the effects of SCH23390 were prevented by a combined treatment with SKF38393. Immunohistochemical analysis indicated that striatal TH(+) neurons expressed D2 and D4 receptors, but not D1 receptors. Moreover, treatment with the α4β2 receptor antagonist dihydro-β-erythroidine (DHβE) (3.2 mg/kg) also increased the number of TH(+) neurons. The evidence that DHβE mimicked the action of SCH23390 in increasing the number of TH(+) neurons supports the hypothesis that activation of D1 receptors controls the number of striatal TH(+) neurons by enhancing the release of acetylcholine. These data demonstrate for the first time that endogenous DA negatively regulates the number of striatal TH(+) neurons by direct and indirect mechanisms mediated by multiple DA receptor subtypes.Carla Letizia BuscetiDomenico BucciGemma MolinaroPaola Di PietroLuca ZangrandiRoberto GradiniRosario MoratallaGiuseppe BattagliaValeria BrunoFerdinando NicolettiFrancesco FornaiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e44025 (2012) |
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Medicine R Science Q Carla Letizia Busceti Domenico Bucci Gemma Molinaro Paola Di Pietro Luca Zangrandi Roberto Gradini Rosario Moratalla Giuseppe Battaglia Valeria Bruno Ferdinando Nicoletti Francesco Fornai Lack or inhibition of dopaminergic stimulation induces a development increase of striatal tyrosine hydroxylase-positive interneurons. |
| description |
We examined the role of endogenous dopamine (DA) in regulating the number of intrinsic tyrosine hydroxylase-positive (TH(+)) striatal neurons using mice at postnatal day (PND) 4 to 8, a period that corresponds to the developmental peak in the number of these neurons. We adopted the strategy of depleting endogenous DA by a 2-day treatment with α-methyl-p-tyrosine (αMpT, 150 mg/kg, i.p.). This treatment markedly increased the number of striatal TH(+) neurons, assessed by stereological counting, and the increase was highly correlated to the extent of DA loss. Interestingly, TH(+) neurons were found closer to the clusters of DA fibers after DA depletion, indicating that the concentration gradient of extracellular DA critically regulates the distribution of striatal TH(+) neurons. A single i.p. injection of the D1 receptor antagonist, SCH23390 (0.1 mg/kg), the D2/D3 receptor antagonist, raclopride (0.1 mg/kg), or the D4 receptor antagonist, L-745,870 (5 mg/kg) in mice at PND4 also increased the number of TH(+) neurons after 4 days. Treatment with the D1-like receptor agonist SKF38393 (10 mg/kg) or with the D2-like receptor agonist, quinpirole (1 mg/kg) did not change the number of TH(+) neurons. At least the effects of SCH23390 were prevented by a combined treatment with SKF38393. Immunohistochemical analysis indicated that striatal TH(+) neurons expressed D2 and D4 receptors, but not D1 receptors. Moreover, treatment with the α4β2 receptor antagonist dihydro-β-erythroidine (DHβE) (3.2 mg/kg) also increased the number of TH(+) neurons. The evidence that DHβE mimicked the action of SCH23390 in increasing the number of TH(+) neurons supports the hypothesis that activation of D1 receptors controls the number of striatal TH(+) neurons by enhancing the release of acetylcholine. These data demonstrate for the first time that endogenous DA negatively regulates the number of striatal TH(+) neurons by direct and indirect mechanisms mediated by multiple DA receptor subtypes. |
| format |
article |
| author |
Carla Letizia Busceti Domenico Bucci Gemma Molinaro Paola Di Pietro Luca Zangrandi Roberto Gradini Rosario Moratalla Giuseppe Battaglia Valeria Bruno Ferdinando Nicoletti Francesco Fornai |
| author_facet |
Carla Letizia Busceti Domenico Bucci Gemma Molinaro Paola Di Pietro Luca Zangrandi Roberto Gradini Rosario Moratalla Giuseppe Battaglia Valeria Bruno Ferdinando Nicoletti Francesco Fornai |
| author_sort |
Carla Letizia Busceti |
| title |
Lack or inhibition of dopaminergic stimulation induces a development increase of striatal tyrosine hydroxylase-positive interneurons. |
| title_short |
Lack or inhibition of dopaminergic stimulation induces a development increase of striatal tyrosine hydroxylase-positive interneurons. |
| title_full |
Lack or inhibition of dopaminergic stimulation induces a development increase of striatal tyrosine hydroxylase-positive interneurons. |
| title_fullStr |
Lack or inhibition of dopaminergic stimulation induces a development increase of striatal tyrosine hydroxylase-positive interneurons. |
| title_full_unstemmed |
Lack or inhibition of dopaminergic stimulation induces a development increase of striatal tyrosine hydroxylase-positive interneurons. |
| title_sort |
lack or inhibition of dopaminergic stimulation induces a development increase of striatal tyrosine hydroxylase-positive interneurons. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/6da1b2f0862e41f485d504302ead7c11 |
| work_keys_str_mv |
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| _version_ |
1718423983180742656 |