title: Growth Hormone Deteriorates the Functional Outcome in an Experimental Model of Huntington's Disease Induced by 3-Nitropionic Acid.
abstract: OBJECTIVE
  Growth hormone (GH) has been frequently used to control the aging process in healthy individuals, probably due to its slowing effect on senescence-associated degeneration. Mitochondrial dysfunction is related to the aging process, and one of the chemical models of Huntington's disease is that it can be induced by mitochondrial toxin. To investigate the potential application of GH to modify the progression of Huntington's disease (HD), we examined whether GH can protect the functional deterioration by striatal damage induced by 3-nitropropionic acid (3NP).
  
  
  METHODS
  3NP (63 mg/kg/day) was delivered to Lewis rats by osmotic pumps for five consecutive days, and the rats received intraperitoneal administration of GH or vehicle (saline) throughout the experiment. Neurological deficits and body weight were monitored. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was performed to further determine the mitochondrial activity in cultured N18TG2 neuroblastoma cells in vitro.
  
  
  RESULTS
  3NP-treated rats showed progressive neurologic deficits with striatal damage. Application of GH accelerated behavioral deterioration, particularly between day 3 and day 5, resulting in reduced survival outcome. The body weights of rats given 3NP were decreased, but GH did not affect such decrease compared to the non-treated control group. The effect of GH on cultured neuronal cells was a decrease in the MTT absorbance, suggesting a lower number of cells in a dose dependent pattern.
  
  
  CONCLUSIONS
  Those results suggest that application of GH to a 3NP-induced experimental model of HD deteriorates the progress of functional deficits, possibly disturbing mitochondrial activities.
authors.affiliation: Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea ; Program in Neuroscience, Seoul National University, Seoul, Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Park
authors.affiliation: Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea ; Program in Neuroscience, Seoul National University, Seoul, Korea.
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Woo-Seok
authors.initials: WS
authors.lastname: Im
authors.affiliation: Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea ; Program in Neuroscience, Seoul National University, Seoul, Korea.
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
keywords: 3-nitropropionic acid; Growth hormone; Huntington’s disease; Mitochondria