Poster Presentation The International Congress of Neuroendocrinology 2014

Title: Crif1-deficiency causes progressive degeneration of dopaminergic neurons and Parkinsonian behavioral abnormalities with loss of appetite in mice . (#158)

Jun Young Heo 1 2 , Jung Su Han , yunseon jang , Su Jung Kim 1 , Jung Im Kim 1 , Minho Shong 3 , Gi Ryang Kweon 1 4
  1. Biochemistry, Chungnam National University School of Medicine, , Daejeon , Korea
  2. Brain Research Institute, Chungnam National University School of Medicine, Daejeon, , Korea
  3. Research Center for Endocrine and Metabolic Diseases, Department of Internal Medicine , , Chungnam National University School of Medicine,, Daejeon,, Korea
  4. Research Institute for Medical Science, Chungnam National University School of Medicine, , Daejeon, , Korea

Parkinson’s disease (PD), which is caused by the loss of specific groups of dopaminergic neurons, is associated with complex molecular and behavioral abnormalities. Although mitochondrial dysfunctions have been associated with PD, the key target molecule linking mitochondrial function to Parkinsonian symptoms remains unknown. Here, we reveal that dopaminergic neuron-specific deletion of the Crif1 gene, which encodes a protein involved in the production of mitochondrial DNA, leads to the selective death of dopaminergic neurons specifically in the substantia nigra but not in the ventral tegmental area. Molecular, behavioral, and pharmacological analyses revealed that Crif1-null mice have a broad range of symptoms similar to those of PD patients, including increased α-synuclein levels and behavioral abnormalities characterized by slow movement, rigidity, and resting tremor that may be rescued by L-DOPA (a putative medication for PD). Furthermore, DATCrif1 mice shown to loss of their body weight and food intake, seems to affected by hypothalamic dysfunction in serotonergic circuit. Our findings indicate that interruption of Crif1-dependent mitochondrial function triggers the selective degeneration of dopaminergic neurons and shown to nonmotor symptoms of PD,  suggesting a novel therapeutic target mechanism for PD.