Low-frequency (1Hz) repetitive transcranial magnetic stimulation (rTMS) reverses Aβ1–42-mediated memory deficits in rats

Abstract

Accumulating evidence shows the disruption of hippocampal neurotrophins secretion leads to memory deficits in Alzheimer's disease (AD) animal models. Invasive injection of exogenous neurotrophins into hippocampus reverses spatial memory deficits, but its clinical application is limited by traumatic brain injury during the injection procedure. Notably, recent studies have demonstrated that noninvasive repetitive transcranial magnetic stimulation (rTMS) increases endogenous neurotrophins contents in the brain of normal rats. Whether low-frequency rTMS can reverse Aβ1–42-mediated decrease in hippocampal neurotrophins contents and spatial memory impairment is still unclear. Here, we reported that severe deficit in long-term potentiation (LTP) and spatial memory were observed in an Aβ1–42-induced toxicity rat model. Furthermore, neurotrophins (NGF and BDNF) and NMDA-receptor levels were decreased after Aβ injection. However, low-frequency rTMS markedly reversed the decrease in neurotrophins contents. And the rTMS-induced increment of neurotrophins up-regulated hippocampal NMDA-receptor expression. Moreover, low-frequency rTMS rescued deficits in LTP and spatial memory of rats with Aβ-injection. These results indicate that low-frequency rTMS noninvasively and effectively increases hippocampal neurotrophins and NMDA-receptor contents in Aβ1–42-induced toxicity model rats, which helps to enhance hippocampal LTP and reverses Aβ1–42-mediated memory deficits.