Repetitive transcranial magnetic stimulation protects mice against 6-OHDA-induced Parkinson's disease symptoms by regulating brain amyloid β1-42 level

Mol Cell Biochem. 2019 Aug;458(1-2):71-78. doi: 10.1007/s11010-019-03531-w. Epub 2019 Apr 19.


Repetitive transcranial magnetic stimulation (rTMS) is a technique protecting neurons against diverse neurodegenerative disorders by delivering magnetic stimuli into the brain through the intact scalp. In the current study, the protection effect of rTMS on Parkinson's disease (PD) and the associated mechanism driving the treatment were explored. The PD symptoms were induced using 6-OHDA in mice, and the effect of rTMS of two frequencies (1 Hz and 10 Hz) on the cognitive behaviors and neuron viability was detected. Afterwards, the level of Aβ1-42 and activity of MKK7-ERK-Fos-APP axis under the administration of rTMS were recorded as well. The intracranial injection of 6-OHDA impaired the cognitive behaviors of the mice in the test of Morris water maze as well as reducing the viability and number of neurons in PD mice. After the treatment of rTMS of both frequencies, the cognitive function of mice was improved and the neuron viability and number were restored in mice brain tissues. The administration of rTMS also increased the cerebrospinal fluid (CSF) level of Aβ1-42 in PD mice, which was accompanied by the suppressed levels of p-MKK7, p-ERK1/2, p-c-Fos, and APP. Moreover, the effect of rTMS on mice nerve system was all exerted in a frequency-dependent manner. In conclusion, the findings outlined in the current study affirmed the protection effect of rTMS against PD. The anti-PD function of rTMS was associated with the suppression of MKK7-ERK-Fos-APP axis, which subsequently resulted in the increased CSF Aβ1-42 level and decreased brain Aβ1-42 level.

Keywords: APP; Aβ1–42; MKK7; Parkinson’s disease; Repetitive transcranial magnetic stimulation.

MeSH terms

  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Animals
  • Brain* / metabolism
  • Brain* / pathology
  • Brain* / physiopathology
  • Maze Learning / drug effects*
  • Mice
  • Neurons / metabolism
  • Neurons / pathology
  • Oxidopamine / toxicity*
  • Parkinson Disease, Secondary* / metabolism
  • Parkinson Disease, Secondary* / pathology
  • Parkinson Disease, Secondary* / physiopathology
  • Parkinson Disease, Secondary* / therapy
  • Peptide Fragments / cerebrospinal fluid*
  • Transcranial Magnetic Stimulation


  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Oxidopamine