PMID:16624565

Citation	Pisani, A, Martella, G, Tscherter, A, Costa, C, Mercuri, NB, Bernardi, G, Shen, J and Calabresi, P (2006) Enhanced sensitivity of DJ-1-deficient dopaminergic neurons to energy metabolism impairment: role of Na+/K+ ATPase. Neurobiol. Dis. 23:54-60
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.
Links	PubMed Online version:10.1016/j.nbd.2006.02.001
Keywords	Animals; Cell Hypoxia/physiology; Disease Models, Animal; Dopamine/metabolism; Energy Metabolism/drug effects; Energy Metabolism/physiology; Enzyme Inhibitors/pharmacology; Glucose/deficiency; Membrane Potentials/drug effects; Membrane Potentials/physiology; Mice; Mice, Knockout; Neurons/drug effects; Neurons/metabolism; Oncogene Proteins/deficiency; Oncogene Proteins/genetics; Organ Culture Techniques; Ouabain/pharmacology; Parkinson Disease/genetics; Parkinson Disease/metabolism; Patch-Clamp Techniques; Rotenone/pharmacology; Sodium-Potassium-Exchanging ATPase/metabolism; Substantia Nigra/drug effects; Substantia Nigra/metabolism; Uncoupling Agents/pharmacology
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