Aluminum impairs hippocampal long-term potentiation in rats in vitro and in vivo.
Although aluminum (Al) contributes to a variety of cognitive dysfunctions and mental diseases, the underlying mechanisms of Al interactions with the nervous system are still unknown. We have studied the action of Al on synaptic transmission and long-term potentiation (LTP) by performing electrophysiological recordings both in vivo, using freely moving animals, and in vitro, using hippocampal slices. In vivo recordings of the population spikes (PSs) of dentate gyrus granule cells in response to medial perforant path stimulation were performed on both acutely and chronically (Al each day for 5 days) intraventricularly injected animals. Acute Al-infusion (calculated brain concentrations of 0.27, 0.68, and 2.7 micrograms/ml) had no influence on baseline values. Al at 0.27 microgram/ml did not alter the induction and maintenance of LTP, but 0.68 and especially 2.7 micrograms/ml Al lead to a reduction in LTP, and the potentiation declined to baseline within 2 h. In chronic animals their neuronal responsiveness was reduced and in 30% of the rats the PS was completely lost. High-frequency tetanization failed to induce LTP. In slices, field potentials were evoked stimulating Schaffer collaterals and recording pyramidal cells of the CA1 region. Bath application of 0.68 microgram/ml Al increased the baseline amplitude of the PS slightly, whereas 2.7 micrograms/ml decreased the amplitude and concentrations > 5.4 micrograms/ml blocked the PS completely. Induction of LTP in the presence of 0.68 microgram/ml Al led to a smaller increase of the PS amplitude compared to controls, but the duration of LTP was not affected. In the presence of 2.7 micrograms/ml Al LTP was further reduced and declined to baseline levels within 60 min. Given that LTP is a form of synaptic plasticity underlying some forms of learning, our data suggest that both preparations are suitable models for investigating actions of Al-induced neurotoxicity.
Platt
B
B
New York State Department of Health, Wadsworth Center for Laboratories and Research, Albany 12201, USA.
Carpenter
D O
DO
Büsselberg
D
D
Reymann
K G
KG
Riedel
G
G
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000535:Aluminum