Altered Cholinergic Metabolism in Rat CNS Following Aluminum Exposure: Implications on Learning Performance

Abstract

The effects of Al on the central cholinergic system have been studied. Al, at a dose of 10 mg/kg of body weight/day for 4 weeks, had a deleterious effect on the activities of biosynthetic (choline acetyltransferase) and hydrolytic (acetylcholinesterase) enzymes of the neurotransmitter acetylcholine. The levels of acetylcholine were also significantly lowered in different brain regions at the end of the dose regimen. There was a significant decrease in high‐affinity choline uptake following Al exposure. Muscarinic acetylcholine receptor binding studies revealed a decreased number of binding sites (Bmax), with the maximum effects being manifested in the hippocampus. Exogenous addition of 10 µM desferrioxamine restored the muscarinic receptor binding completely. The impaired cholinergic functioning had severe effects on cognitive functions. Neurobehavioral deficits were manifested in terms of decreased active (52%) and passive (73.30%) avoidance tests. The results suggest that Al exerts its toxic effects by altering cholinergic transmission, which is ultimately reflected in neurobehavioral deficits.

Does neurotransmission impairment accompany aluminium neurotoxicity?

“…Choline is then covalently linked with an activated acetyl unit from acetylCoA to form acetylcholine by choline O-acetyltransferase. In spite of some authors reporting no effects of aluminium on this enzyme activity [114][115][116][117], a decline of choline Oacetyltransferase activity following in vivo exposure to aluminium has been consistently observed [93,[118][119][120][121][122][123][124][125][126][127], which can be, in part, warranted by cyclooxygenase-2 induced reduction of choline O-acetyltransferase protein expression [128]. In fact, gene up-and down-regulation of cyclooxygenase-2 and choline O-acetyltransferase, respectively, have been detected in aluminium-treated cells in culture [79].…”

“…Intriguingly, no remarkable changes in acetylcholine content in different regions of the brain following distinct protocols of exposure were observed by the majority of investigators, with the exception of Julka et al [125]. These researchers performed a detailed investigation into the effects of aluminium exposure on the presynaptic cholinergic system of the rat, which included the analysis of enzymatic activities responsible for the synthesis and degradation of acetylcholine, choline uptake, quantification of acetylcholine receptors and the synaptic vesicle content in acetylcholine.…”

Aluminum, NO, and nerve growth factor neurotoxicity in cholinergic neurons

“…Early data concerning Al-encephalopathy in rats are discrepant. However, recent reports demonstrated that intracerebral injections of A1 suppressed brain cholinergic makers along with appearance of neurobehavioral deficits (Table I) (Julka et al, 1995). Cultured hippocampal neurons died after exposure to low Al concentrations (Brenner and Yoon, 1994).…”

“…Extracellular Al was found to inhibit Ca 2ϩ entry through voltage-gated Ca-channels (Koenig and Jope, 1987). Accordingly, Al was reported to inhibit Caevoked (quantal) ACh release both in whole brain, isolated nerve terminals, and neuroblastoma cells (Julka et al, 1995;Bielarczyk et al, 1998;Jankowska et al, 2000). It also competed with inhibitory effects of verapamil and other antagonists of Ca-channels on ACh release.…”

Memory performance, brain excitatory amino acid and acetylcholinesterase activity of chronically aluminum exposed mice in response to soy isoflavones treatment

“…Aluminum is considered a potential etiological factor in Alzheimer's disease because Al might induce characteristic brain neurofi brillary of the disease (ElRahman, 2003). The administration of Al compounds causes neuroanatomical and neurochemical alterations in the brain such as neurofi lament accumulation (Simpson et al, 1985), neuron loss (Ghetti et al, 1985) and suppression of the cholinergic system (Julka et al, 1995;Bielarczyk et al, 2003). In addition, Al exposure was found to cause glutamate system impairment such as decreases of glutamate contents in brain (Exley, 1999;Nayak and Chatterjee, 2001).…”