Aluminum-Induced Electrophysiological Variation, Synaptic Plasticity Impairment, and Related Mechanism

Aluminum, an environmentally abundant non-redox trivalent cation, has long been reported to alter blood-brain barrier and gets deposited in different regions of the brain. Many reports strongly indicated that Al had an adverse impact on the central nervous system (CNS), particularly on cognitive ability. Until now, studies in animal models and cell cultures have revealed that Al exposure results in altered behavioral performance and memory damage. The present paper reviews the scientific literature linking aluminum and the impairment of electrophysiological variation and synaptic plasticity. The focus is on the changes of electrical excitability, voltage-operated ion channels, and synaptic plasticity induced by aluminum. A detailed mechanism of the role of aluminum in hippocampal LTP which is the most widely studied example of synaptic plasticity is highlighted. Evidence revealed that glutamate-NO-cGMP, PLC, Ca²⁺-CaM-CaMKII, MAPK, and Wnt pathway may be important in the mechanism underlying Al-induced long-term memory impairment. Further studies are required to establish the upstream activators and downstream effectors of these cascades and to answer how so many signaling cascades relate to the other signaling processes that might be involved in the Al-induced inhibition of synaptic plasticity.