Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1.

The manifestations of Parkinson's disease are caused by reduced dopaminergic innervation of the striatum. Loss-of-function mutations in the DJ-1 gene cause early-onset familial parkinsonism. To investigate a possible role for DJ-1 in the dopaminergic system, we generated a mouse model bearing a germline disruption of DJ-1. Although DJ-1(-/-) mice had normal numbers of dopaminergic neurons in the substantia nigra, evoked dopamine overflow in the striatum was markedly reduced, primarily as a result of increased reuptake. Nigral neurons lacking DJ-1 were less sensitive to the inhibitory effects of D2 autoreceptor stimulation. Corticostriatal long-term potentiation was normal in medium spiny neurons of DJ-1(-/-) mice, but long-term depression (LTD) was absent. The LTD deficit was reversed by treatment with D2 but not D1 receptor agonists. Furthermore, DJ-1(-/-) mice displayed hypoactivity in the open field. Collectively, our findings suggest an essential role for DJ-1 in dopaminergic physiology and D2 receptor-mediated functions.

Pubmed ID: 15721235


  • Goldberg MS
  • Pisani A
  • Haburcak M
  • Vortherms TA
  • Kitada T
  • Costa C
  • Tong Y
  • Martella G
  • Tscherter A
  • Martins A
  • Bernardi G
  • Roth BL
  • Pothos EN
  • Calabresi P
  • Shen J



Publication Data

February 17, 2005

Associated Grants


Mesh Terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Age Factors
  • Animals
  • Behavior, Animal
  • Blotting, Southern
  • Blotting, Western
  • Cell Count
  • Cerebral Cortex
  • Disease Models, Animal
  • Dopamine
  • Dopamine Agonists
  • Dopamine Plasma Membrane Transport Proteins
  • Electric Stimulation
  • Electrochemistry
  • Excitatory Postsynaptic Potentials
  • Germ-Line Mutation
  • Humans
  • Hypokinesia
  • Immunohistochemistry
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins
  • Neurons
  • Oncogene Proteins
  • Parkinsonian Disorders
  • Quinpirole
  • RNA, Messenger
  • Radioligand Assay
  • Receptors, Dopamine D2
  • Reverse Transcriptase Polymerase Chain Reaction
  • Substantia Nigra
  • Tyrosine 3-Monooxygenase