title: Ischemia induces different levels of hypoxia inducible factor-1α protein expression in interneurons and pyramidal neurons.
abstract: BACKGROUND
  Pyramidal (glutamatergic) neurons and interneurons are morphologically and functionally well defined in the central nervous system. Although it is known that glutamatergic neurons undergo immediate cell death whereas interneurons are insensitive or survive longer during cerebral ischemia, the protection mechanisms responsible for this interneuronal survival are not well understood. Hypoxia inducible factor-1 (HIF-1) plays an important role in protecting neurons from hypoxic/ischemic insults. Here, we studied the expression of HIF-1α, the regulatable subunit of HIF-1, in the different neuronal phenotypes under in vitro and in vivo ischemia.
  
  
  RESULTS
  In a primary cortical culture, HIF-1α expression was observed in neuronal somata after hypoxia (1% oxygen) in the presence of 5 or 25 mM glucose but not under normoxia (21% oxygen). Interestingly, only certain MAP2-positive neurons containing round somata (interneuron-like morphology) co-localized with HIF-1α staining. Other neurons such as pyramidal-like neurons showed no expression of HIF-1α under either normoxia or hypoxia. The HIF-1α positive neurons were GAD65/67 positive, confirming that they were interneuron-type cells. The HIF-1α expressing GAD65/67-positive neurons also possessed high levels of glutathione. We further demonstrated that ischemia induced significant HIF-1α expression in interneurons but not in pyramidal neurons in a rat model of middle cerebral artery occlusion.
  
  
  CONCLUSIONS
  These results suggest that HIF-1α protein expression induced by ischemia is neuron-type specific and that this specificity may be related to the intracellular level of glutathione (GSH).
authors.forename: Prabhu
authors.initials: P
authors.lastname: Ramamoorthy
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, 5064 Malott, Lawrence, KS 66045, USA. hshi@ku.edu.
authors.forename: Honglian
authors.initials: H
authors.lastname: Shi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death; D015687:Cell Hypoxia / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000473:pathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D007395:Interneurons / Q000378:metabolism*; D008297:Male; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D005978:Glutathione