Effects of aluminium exposure on brain glutamate and GABA systems: an experimental study in rats

It has been postulated that the neurotoxic effects of aluminium could be me diated through glutamate, an excitatory amino acid. Hence the effects of al uminium administration (at a dose of 4.2 mg/kg body weight daily as alumini um chloride, hexahydrate, intraperitoneally, for 4 weeks) on glutamate and gamma -amino butyrate (GABA), an inhibitory amino acid, and related enzyme activities in different regions of the brain were studied in albino rats. T he glutamate level increased significantly in the cerebrum, thalamic area, midbrain-hippocampal region and cerebellum in response to in vivo aluminium exposure. The aluminium insult also caused significant increases in glutam ate alpha -decarboxylase activity in all the brain regions. However, on alu minium insult, the GABA content was not significantly changed except in the thalamic area, where it was elevated. On the contrary, the GABA-T activiti es of all the regions were reduced significantly in all regions except the midbrain-hippocampal region. However, the succinic semi-aldehyde content of all brain regions increased, often significantly. The aluminium-induced mo dification of the enzyme activities may be either due to the direct impact of aluminium or due to aluminium-induced changes in the cellular environmen t. The aluminium-induced differential regional accumulation of glutamate or other alterations in enzymes of the glutamate-GABA system may be one of th e causes of aluminium-induced neurotoxicity. (C) 2001 Elsevier Science Ltd. All rights reserved.