title: Intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in ALS mice.
abstract: BACKGROUND
  Patients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia model and it is possible that chronic intermittent hypoxia exerts effects via a different molecular mechanism from that of sustained hypoxia. No study has yet shown that hypoxia (either chronic intermittent or sustained) can affect the loss of motor neurons or cognitive function in an in vivo model of ALS.
  
  
  OBJECTIVE
  To evaluate the effects of chronic intermittent hypoxia on motor and cognitive function in ALS mice.
  
  
  METHODS
  Sixteen ALS mice and 16 wild-type mice were divided into 2 groups and subjected to either chronic intermittent hypoxia or normoxia for 2 weeks. The effects of chronic intermittent hypoxia on ALS mice were evaluated using the rotarod, Y-maze, and wire-hanging tests. In addition, numbers of motor neurons in the ventral horn of the spinal cord were counted and western blot analyses were performed for markers of oxidative stress and inflammatory pathway activation.
  
  
  RESULTS
  Compared to ALS mice kept in normoxic conditions, ALS mice that experienced chronic intermittent hypoxia had poorer motor learning on the rotarod test, poorer spatial memory on the Y-maze test, shorter wire hanging time, and fewer motor neurons in the ventral spinal cord. Compared to ALS-normoxic and wild-type mice, ALS mice that experienced chronic intermittent hypoxia had higher levels of oxidative stress and inflammation.
  
  
  CONCLUSIONS
  Chronic intermittent hypoxia can aggravate motor neuronal death, neuromuscular weakness, and probably cognitive dysfunction in ALS mice. The generation of oxidative stress with activation of inflammatory pathways may be associated with this mechanism. Our study will provide insight into the association of hypoxia with disease progression, and in turn, the rationale for an early non-invasive ventilation treatment in patients with ALS.
authors.affiliation: Department of Neurology, Seoul National University, College of Medicine, Seoul, Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Kim
authors.forename: Heejaung
authors.initials: H
authors.lastname: Kim
authors.forename: Jeong-Seon
authors.initials: JS
authors.lastname: Lee
authors.forename: Kyung Seok
authors.initials: KS
authors.lastname: Park
authors.forename: Gye Sun
authors.initials: GS
authors.lastname: Jeon
authors.forename: Jeeheun
authors.initials: J
authors.lastname: Shon
authors.forename: Suk-Won
authors.initials: SW
authors.lastname: Ahn
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Sung
authors.forename: Kwang-Woo
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology*; D053580:Muscle Strength; D018384:Oxidative Stress; D011597:Psychomotor Performance; D045442:Rotarod Performance Test; D015398:Signal Transduction