title: Experimental diabetes mellitus type 1 increases hippocampal content of kynurenic acid in rats.
abstract: BACKGROUND
  Diabetes mellitus (DM) is frequently associated with peripheral and central complications and has recently emerged as a risk factor for cognitive impairment and dementia. Kynurenic acid (KYNA), a unique tryptophan derivative, displays pleiotropic effects including blockade of ionotropic glutamate and α7 nicotinic receptors. Here, the influence of experimental diabetes on KYNA synthesis was studied in rat brain.
  
  
  METHODS
  DM was induced by i.p. administration of streptozotocin (STZ). Five weeks later, KYNA content and the activity of semi-purified kynurenine aminotransferases (KATs) were measured in frontal cortex, hippocampus and striatum of diabetic and insulin-treated rats, using HPLC-based methods.
  
  
  RESULTS
  Hippocampal but not cortical or striatal KYNA concentration was considerably increased during DM, either untreated or treated with insulin (220% and 170% of CTR, respectively). The activity of kynurenine aminotransferase I (KAT I) was not affected by DM in all of the studied structures. KAT II activity was moderately increased in cortex (145% of CTR) and hippocampus (126% of CTR), but not in striatum of diabetic animals. Insulin treatment normalized cortical but not hippocampal KAT II activity.
  
  
  CONCLUSIONS
  A novel factor potentially implicated in diabetic hippocampal dysfunction has been identified. Observed increase of KYNA level may stem from the activation of endogenous neuroprotection, however, it may also have negative impact on cognition.
authors.affiliation: Medical University of Lublin, Lublin, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Chmiel-Perzyńska
authors.affiliation: Medical University of Lublin, Lublin, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Perzyński
authors.affiliation: Medical University of Lublin, Lublin, Poland; Institute of Agricultural Medicine, Lublin, Poland. Electronic address: emurbanska@poczta.onet.pl.
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Urbańska
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003071:Cognition / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007736:Kynurenic Acid / Q000378:metabolism*; D051381:Rats; D013311:Streptozocin; D000637:Transaminases / Q000378:metabolism
chemical_list: D007328:Insulin; D013311:Streptozocin; D000637:Transaminases; C021481:kynurenine-oxoglutarate transaminase; D007736:Kynurenic Acid
keywords: Diabetes mellitus type 1; Kynurenic acid; Memory; Neurodegeneration