title: Protective effects of glucose-6-phosphate dehydrogenase on neurotoxicity of aluminium applied into the CA1 sector of rat hippocampus.
abstract: OBJECTIVE
  Aluminum (Al) toxicity is closely linked to the pathogenesis of Alzheimer's disease (AD). This experimental study was aimed to investigate the active avoidance behaviour of rats after intrahippocampal injection of Al, and biochemical and immunohistochemical changes in three bilateral brain structures namely, forebrain cortex (FBCx), hippocampus and basal forebrain (BF).
  
  
  METHODS
  Seven days after intra-hippocampal (CA1 sector) injection of AlCl3 into adult male Wistar rats they were subjected to two-way active avoidance (AA) tests over five consecutive days. Control rats were treated with 0.9% w/v saline. The animals were decapitated on the day 12 post-injection. The activities of acetylcholinesterase (AChE) and glucose-6-phosphate dehydrogenase (G6PDH) were measured in the FBCx, hippocampus and BF. Immunohistochemical staining was performed for transferrin receptors, amyloid β and tau protein.
  
  
  RESULTS
  The activities of both AChE and G6PDH were found to be decreased bilaterally in the FBCx, hippocampus and basal forebrain compared to those of control rats. The number of correct AA responses was reduced by AlCl3 treatment. G6PDH administered prior to AlCl 3 resulted in a reversal of the effects of AlCl3 on both biochemical and behavioural parameters. Strong immunohistochemical staining of transferrin receptors was found bilaterally in the FBCx and the hippocampus in all three study groups. In addition, very strong amyloid β staining was detected bilaterally in all structures in AlCl3-treated rats but was moderate in G6PDH/AlCl3-treated rats. Strong tau staining was noted bilaterally in AlCl3-treated rats. In contrast, tau staining was only moderate in G6PDH/AlCl3-treated rats.
  
  
  CONCLUSIONS
  Our findings indicated that the G6PDH alleviated the signs of behavioural and biochemical effects of AlCl3-treatment suggesting its involvement in the pathogenesis of Al neurotoxicity and its potential therapeutic benefit. The present model could serve as a useful tool in AD investigations.
authors.affiliation: Military Medical Academy, Institute for Medical Research, Belgrade, Serbia.
authors.forename: Marina D
authors.initials: MD
authors.lastname: Jovanović
authors.forename: Ankica
authors.initials: A
authors.lastname: Jelenković
authors.forename: Ivana D
authors.initials: ID
authors.lastname: Stevanović
authors.forename: Dubravko
authors.initials: D
authors.lastname: Bokonjić
authors.forename: Miodrag
authors.initials: M
authors.lastname: Colić
authors.forename: Natasa
authors.initials: N
authors.lastname: Petronijević
authors.forename: Danica B
authors.initials: DB
authors.lastname: Stanimirović
mesh_terms: D000110:Acetylcholinesterase / Q000494:pharmacology*; D000535:Aluminum / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011990:Receptors, Transferrin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D011990:Receptors, Transferrin; D000535:Aluminum; D005954:Glucosephosphate Dehydrogenase; D000110:Acetylcholinesterase
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