Effects of Continuous Theta Burst Stimulation on Behavior and NMDA Receptor Subunits in the Trimethyltin-Induced Alzheimer’s-like Disease Model

Abstract

Background: Trimethyltin (TMT)-induced neurodegeneration leads to molecular and behavioral changes resembling those of Alzheimer’s disease (AD), making it a relevant model for investigating potential therapeutic interventions. Continuous theta burst stimulation (cTBS) has shown promise in psychiatric and neurological disorders but remains largely unexplored in AD models. Methods: Adult male Wistar rats were divided into four experimental groups: intact, TMT (8 mg/kg, ip) and TMT treated with cTBS or a sham protocol for three weeks. The open field test and novel object recognition test were used to assess anxiety-like behavior, memory, and learning, respectively. The extent of microgliosis in the hippocampus was assessed by immunohistochemistry, while protein expression was estimated by Western blot. Results: cTBS improved TMT-mediated changes in anxiety-like behavior, learning, and memory and reduced microgliosis in the CA1 hippocampal region. Both TMT and cTBS affected NMDAR subunits, with the most significant finding being a cTBS-mediated decrease in NR2B, which was previously increased by TMT. Conclusions: These are the first data on the beneficial effects of cTBS on behavioral and molecular changes in a model of neurodegeneration that mimics some of the key aspects of AD pathology. Further research is needed to clarify the therapeutic potential of cTBS in AD treatment.