Dystonia is a hyperkinetic movement disorder, whose pathogenesis is related to a network disfunction of basal ganglia, specifically to a disrupted equilibrium between direct and indirect pathways. Phosphodiesterase 10A (PDE10A), a key enzyme in the catabolism of cAMP and cGMP, is localized within Medium Spiny Neurons in the striatum and in their axon terminals in the substantia nigra pars reticulata and external globus pallidus. Therefore PDE10A may represent a map of the balance between the direct and indirect pathways in normal and pathological basal ganglia conditions. Early-onset torsion dystonia (DYT1), the most common form of dystonia, is an autosomal disease caused by a deletion in the gene encoding protein TorsinA. We investigate changes of PDE10A immunoreactivity in basal ganglia of TorsinA DYT1 mice, a transgenic model of DYT1, comparing results between control mice and mice carrying either human wilde-type torsinA(hWT) or mutant torsinA(hMT). In control mice PDE10A immunoreactivity was observed in neuronal bodies and in the neuropil throughout the caudate-putamen, in the neuropil of the globus pallidus and in substantia nigra pars reticulata. Our study revealed that PDE10A expression was increased in the globus pallidus of hWT mice, while in substantia nigra PDE10 immunoreactivity was overexpressed both in hWT mice and in hMT mice. PDE10A up-regulation may lead to a decreased activation in the indirect striatum-external globus pallidus pathway. The increase of PDE10A also in the substantia nigra suggests that dystonia may express a functional up-regulation of basal ganglia circuits both in the direct and indirect pathway.
Torsin-a DYT1-transgenic mice overexpress phosphodiesterase 10A in striato-nigral and striato-pallidal pathways / V., D'Angelo; V., Castelli; F., Palunbo; Giorgi, Mauro; T., Schirinzi; Cardarelli, Silvia; A., Pisani; G., Sancesario. - STAMPA. - (2013). (Intervento presentato al convegno Congresso società italiana di neuroscienze tenutosi a Roma nel 3-5 Ottobre 2013).
Torsin-a DYT1-transgenic mice overexpress phosphodiesterase 10A in striato-nigral and striato-pallidal pathways.
GIORGI, MAURO;CARDARELLI, SILVIA;
2013
Abstract
Dystonia is a hyperkinetic movement disorder, whose pathogenesis is related to a network disfunction of basal ganglia, specifically to a disrupted equilibrium between direct and indirect pathways. Phosphodiesterase 10A (PDE10A), a key enzyme in the catabolism of cAMP and cGMP, is localized within Medium Spiny Neurons in the striatum and in their axon terminals in the substantia nigra pars reticulata and external globus pallidus. Therefore PDE10A may represent a map of the balance between the direct and indirect pathways in normal and pathological basal ganglia conditions. Early-onset torsion dystonia (DYT1), the most common form of dystonia, is an autosomal disease caused by a deletion in the gene encoding protein TorsinA. We investigate changes of PDE10A immunoreactivity in basal ganglia of TorsinA DYT1 mice, a transgenic model of DYT1, comparing results between control mice and mice carrying either human wilde-type torsinA(hWT) or mutant torsinA(hMT). In control mice PDE10A immunoreactivity was observed in neuronal bodies and in the neuropil throughout the caudate-putamen, in the neuropil of the globus pallidus and in substantia nigra pars reticulata. Our study revealed that PDE10A expression was increased in the globus pallidus of hWT mice, while in substantia nigra PDE10 immunoreactivity was overexpressed both in hWT mice and in hMT mice. PDE10A up-regulation may lead to a decreased activation in the indirect striatum-external globus pallidus pathway. The increase of PDE10A also in the substantia nigra suggests that dystonia may express a functional up-regulation of basal ganglia circuits both in the direct and indirect pathway.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.