title: A bile acid protects against motor and cognitive deficits and reduces striatal degeneration in the 3-nitropropionic acid model of Huntington's disease.
abstract: There is currently no effective treatment for Huntington's disease (HD), a progressive, fatal, neurodegenerative disorder characterized by motor and cognitive deterioration. It is well established that HD is associated with perturbation of mitochondrial energy metabolism. Tauroursodeoxycholic acid (TUDCA), a naturally occurring bile acid, can stabilize the mitochondrial membrane, inhibit the mitochondrial permeability transition, decrease free radical formation, and derail apoptotic pathways. Here we report that TUDCA significantly reduced 3-nitropropionic acid (3-NP)-mediated striatal neuronal cell death in cell culture. In addition, rats treated with TUDCA exhibited an 80% reduction in apoptosis and in lesion volumes associated with 3-NP administration. Moreover, rats which received a combination of TUDCA + 3-NP exhibited sensorimotor and cognitive task performance that was indistinguishable from that of controls, and this effect persisted at least 6 months. Bile acids have traditionally been used as therapeutic agents for certain liver diseases. This is the first demonstration, however, that a bile acid can be delivered to the brain and function as a neuroprotectant and thus may offer potential therapeutic benefit in the treatment of certain neurodegenerative diseases.
authors.affiliation: Graduate Program in Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Keene
authors.forename: C M
authors.initials: CM
authors.lastname: Rodrigues
authors.forename: T
authors.initials: T
authors.lastname: Eich
authors.forename: C
authors.initials: C
authors.lastname: Linehan-Stieers
authors.forename: A
authors.initials: A
authors.lastname: Abt
authors.forename: B T
authors.initials: BT
authors.lastname: Kren
authors.forename: C J
authors.initials: CJ
authors.lastname: Steer
authors.forename: W C
authors.initials: WC
authors.lastname: Low
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003071:Cognition / Q000187:drug effects*; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006816:Huntington Disease / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control / Q000523:psychology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009043:Motor Activity / Q000187:drug effects*; D009410:Nerve Degeneration / Q000517:prevention & control*; D009498:Neurotoxins / Q000633:toxicity*; D009574:Nitro Compounds; D011422:Propionates / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D013655:Taurochenodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; C015392:3-nitropropionic acid