Dystonia pathophysiology has been partly linked to downregulation and dysfunction of dopamine D2 receptors in striatum. We aimed to investigate the possible morpho-structural correlates of D2 receptor downregulation in the striatum of a DYT1 Tor1a mouse model. Adult control Tor1a+/+ and mutant Tor1a+/− mice were used. The brains were perfused and free-floating sections of basal ganglia were incubated with polyclonal anti-D2 antibody, followed by secondary immune-fluorescent antibody. Confocal microscopy was used to detect immune-fluorescent signals. The same primary antibody was used to evaluate D2 receptor expression by western blot. The D2 receptor immune-fluorescence appeared circumscribed in small disks (~0.3–0.5 μm diameter), likely representing D2 synapse aggregates, densely distributed in the striatum of Tor1a+/+ mice. In the Tor1a+/− mice the D2 aggregates were significantly smaller (μm2 2.4 ± SE 0.16, compared to μm2 6.73 ± SE 3.41 in Tor1a+/+) and sparse, with ~30% less number per microscopic field, value correspondent to the amount of reduced D2 expression in western blotting analysis. In DYT1 mutant mice the sparse and small D2 synapses in the striatum may be insufficient to “gate” the amount of presynaptic dopamine release diffusing in peri-synaptic space, and this consequently may result in a timing and spatially larger nonselective sphere of influence of dopamine action.

Dystonia: sparse synapses for D2 receptors in striatum of a DYT1 knock-out mouse model / D'Angelo, V.; Paldino, E.; Cardarelli, S.; Sorge, R.; Fusco, F. R.; Biagioni, S.; Mercuri, N. B.; Giorgi, M.; Sancesario, G.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 21:3(2020), pp. 1-12. [10.3390/ijms21031073]

Dystonia: sparse synapses for D2 receptors in striatum of a DYT1 knock-out mouse model

Cardarelli S.;Biagioni S.;Giorgi M.
Penultimo
;
2020

Abstract

Dystonia pathophysiology has been partly linked to downregulation and dysfunction of dopamine D2 receptors in striatum. We aimed to investigate the possible morpho-structural correlates of D2 receptor downregulation in the striatum of a DYT1 Tor1a mouse model. Adult control Tor1a+/+ and mutant Tor1a+/− mice were used. The brains were perfused and free-floating sections of basal ganglia were incubated with polyclonal anti-D2 antibody, followed by secondary immune-fluorescent antibody. Confocal microscopy was used to detect immune-fluorescent signals. The same primary antibody was used to evaluate D2 receptor expression by western blot. The D2 receptor immune-fluorescence appeared circumscribed in small disks (~0.3–0.5 μm diameter), likely representing D2 synapse aggregates, densely distributed in the striatum of Tor1a+/+ mice. In the Tor1a+/− mice the D2 aggregates were significantly smaller (μm2 2.4 ± SE 0.16, compared to μm2 6.73 ± SE 3.41 in Tor1a+/+) and sparse, with ~30% less number per microscopic field, value correspondent to the amount of reduced D2 expression in western blotting analysis. In DYT1 mutant mice the sparse and small D2 synapses in the striatum may be insufficient to “gate” the amount of presynaptic dopamine release diffusing in peri-synaptic space, and this consequently may result in a timing and spatially larger nonselective sphere of influence of dopamine action.
D2 receptors; dopamine volume transmission; dystonia; striatum; synapses
01 Pubblicazione su rivista::01a Articolo in rivista
Dystonia: sparse synapses for D2 receptors in striatum of a DYT1 knock-out mouse model / D'Angelo, V.; Paldino, E.; Cardarelli, S.; Sorge, R.; Fusco, F. R.; Biagioni, S.; Mercuri, N. B.; Giorgi, M.; Sancesario, G.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 21:3(2020), pp. 1-12. [10.3390/ijms21031073]
File allegati a questo prodotto
File Dimensione Formato  
D'Angelo_Dystonia_2020.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 5.38 MB
Formato Adobe PDF
5.38 MB Adobe PDF Visualizza/Apri PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1390245
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 4
social impact