DJ-1 gene mutations lead to an inherited form of early-onset parkinsonism. The function of DJ-1 is unclear, though a neuroprotective role has been postulated. Electrophysiological recordings were made of striatal and dopaminergic nigral neurons both of wild-type (WT) and DJ-1-knockout (DJ-1(-/-)) mice. We assessed the responses of dopaminergic cells to combined oxygen and glucose deprivation (OGD), and to the mitochondrial toxin rotenone. OGD induced a membrane hyperpolarization in nigral neurons from WT mice. Similarly, rotenone hyperpolarized neurons and then a depolarization occurred. In DJ-1(-/-) mice, the OGD-induced hyperpolarization was significantly enhanced. Moreover, rotenone caused a shorter hyperpolarization followed by an irreversible depolarization. To evaluate the involvement of Na+/K+ ATPase, we tested ouabain, a Na+/K+ ATPase inhibitor, on two distinct neuronal subtypes. Compared to WT mice, in dopaminergic neurons from DJ-1(-/-) mice, ouabain induced rapid and irreversible membrane potential changes. Notably, this effect was observed at concentrations that were unable to produce membrane potential shifts on striatal spiny neurons, both from WT and DJ-1(-/-) mice. These findings suggest that DJ-1 loss-of-function enhances vulnerability to energy metabolism alterations, and that nigral neurons are particularly sensitive to Na+/K+ ATPase impairment.

Pisani, A., Martella, G., Tscherter, A., Costa, C., Mercuri, N.b., Bernardi, G., et al. (2006). Enhanced sensitivity of DJ-1-deficient dopaminergic neurons to energy metabolism impairment: role of Na+/K+ ATPase. NEUROBIOLOGY OF DISEASE, 23(1), 54-60 [10.1016/j.nbd.2006.02.001].

Enhanced sensitivity of DJ-1-deficient dopaminergic neurons to energy metabolism impairment: role of Na+/K+ ATPase

PISANI, ANTONIO;MARTELLA, GIUSEPPINA;MERCURI, NICOLA BIAGIO;BERNARDI, GIORGIO;CALABRESI, PAOLO
2006-07-01

Abstract

DJ-1 gene mutations lead to an inherited form of early-onset parkinsonism. The function of DJ-1 is unclear, though a neuroprotective role has been postulated. Electrophysiological recordings were made of striatal and dopaminergic nigral neurons both of wild-type (WT) and DJ-1-knockout (DJ-1(-/-)) mice. We assessed the responses of dopaminergic cells to combined oxygen and glucose deprivation (OGD), and to the mitochondrial toxin rotenone. OGD induced a membrane hyperpolarization in nigral neurons from WT mice. Similarly, rotenone hyperpolarized neurons and then a depolarization occurred. In DJ-1(-/-) mice, the OGD-induced hyperpolarization was significantly enhanced. Moreover, rotenone caused a shorter hyperpolarization followed by an irreversible depolarization. To evaluate the involvement of Na+/K+ ATPase, we tested ouabain, a Na+/K+ ATPase inhibitor, on two distinct neuronal subtypes. Compared to WT mice, in dopaminergic neurons from DJ-1(-/-) mice, ouabain induced rapid and irreversible membrane potential changes. Notably, this effect was observed at concentrations that were unable to produce membrane potential shifts on striatal spiny neurons, both from WT and DJ-1(-/-) mice. These findings suggest that DJ-1 loss-of-function enhances vulnerability to energy metabolism alterations, and that nigral neurons are particularly sensitive to Na+/K+ ATPase impairment.
lug-2006
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26 - NEUROLOGIA
English
Con Impact Factor ISI
Animals; Oncogene Proteins; Glucose; Disease Models, Animal; Enzyme Inhibitors; Mice; Uncoupling Agents; Cell Hypoxia; Energy Metabolism; Mice, Knockout; Sodium-Potassium-Exchanging ATPase; Patch-Clamp Techniques; Dopamine; Rotenone; Parkinson Disease; Neurons; Ouabain; Membrane Potentials; Substantia Nigra; Organ Culture Techniques
Pisani, A., Martella, G., Tscherter, A., Costa, C., Mercuri, N.b., Bernardi, G., et al. (2006). Enhanced sensitivity of DJ-1-deficient dopaminergic neurons to energy metabolism impairment: role of Na+/K+ ATPase. NEUROBIOLOGY OF DISEASE, 23(1), 54-60 [10.1016/j.nbd.2006.02.001].
Pisani, A; Martella, G; Tscherter, A; Costa, C; Mercuri, Nb; Bernardi, G; Shen, J; Calabresi, P
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
NBD_2006_DJ1.pdf

solo utenti autorizzati

Licenza: Non specificato
Dimensione 178.79 kB
Formato Adobe PDF
178.79 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

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/2108/88293
Citazioni
  • ???jsp.display-item.citation.pmc??? 17
  • Scopus 54
  • ???jsp.display-item.citation.isi??? 45
social impact