Vasopressin reverses aluminum-induced impairment of synaptic plasticity in the rat dentate gyrus in vivo

Abstract

Aluminum (Al), an important neurotoxin, contributes to a variety of cognitive dysfunction and mental diseases. Previous studies have demonstrated that Al impairs hippocampal long-term potentiation (LTP) in vitro and in vivo. In the present study, both LTP and LTD (long-term depression) were recorded in the same animal to investigate the Al-induced impairment of synaptic plasticity. Another aim of the present research was to verify whether the impairment of synaptic plasticity induced by Al could be reversed by vasopressin (VP) treatment. Neonatal Wistar rats were exposed to Al from parturition through adulthood (pre- and post-weaning) by the drinking of 0.3% aluminum chloride (AlCl 3) solution. The input–output (I/O) function, paired-pulse reaction (PPR), excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude were measured in the dentate gyrus (DG) of adult rats (60–90 days) in response to stimulation applied to the lateral perforant path. The results showed: (1) Al reduced the amplitudes of both EPSP LTP (control: 132±7%, n=7; Al-exposed: 115±10%, n=8, P<0.05) and PS LTP (control: 242±18%, n=7; Al-exposed: 136±7%, n=8, P<0.01) significantly. The amplitudes of EPSP LTD (control: 82±6%, n=7; Al-exposed: 92±7%, n=8, P<0.05) and PS LTD (control: 81±4%, n=7; Al-exposed: 98±5%, n=8, P<0.05) were also decreased by Al treatment. The Al-induced impairments of PS LTP and PS LTD were more serious than that of EPSP LTP and EPSP LTD. (2) In control rats, VP had an increase in the PS LTP amplitude (control: 242±18%, n=7; control+VP: 358±23%, n=6, P<0.01), while it had no significant effects on PS LTD (control: 81±4%, n=7; control+VP: 76±7%, n=6, P>0.05). (3) In Al-exposed rats, VP had a significant increase in the amplitudes of both PS LTP (Al-exposed: 136±7%, n=8, Al-exposed+VP: 255±16%, n=6, P<0.01) and PS LTD (Al-exposed: 98±5%, n=8; Al-exposed+VP: 81±6%, n=6, P<0.05). After the application of VP, the range of synaptic plasticity (PS LTP+PS LTD) in Al-exposed rats increased from 38% to 174%, which surpassed that in control rats (161%). It was suggested that VP could reverse Al-induced impairment of synaptic plasticity and might be an effective medicine to cure Al-induced neurological disorders.