• Register
Forgot Password

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


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


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