Age-related cerebellar genetic, neuronal and functional impairments are reversed by specific magnetic stimulation protocols

Abstract

Age-related cognitive decline reflects progressive atrophic changes that advance through broad neural networks. There is no effective treatment. However, brain ageing is not homogenous, so treating the earliest-affected circuits may be successful in reversing and/or preventing ongoing neuronal atrophy and therefore cognitive decline. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive technique that modulates cortical excitability, induces activity-dependent neuronal plasticity. Here we investigate short- and long-term effects of low intensity rTMS (LI-rTMS) on the cerebellum, which is adversely affected early during ageing. With age, cerebellar genes related to inflammation are strongly upregulated, whereas processes of synaptic-maintenance are reduced. Both abnormalities are rapidly corrected by LI-rTMS in a protocol-dependent manner. In parallel, LI-rTMS increases neuronal spine density and dendritic complexity, in association with improved spatial memory in both young adult and aged mice. These responses of the ageing cerebellum to low-intensity magnetic stimulation are extremely encouraging for treating age-related cognitive decline, but reinforce that appropriate stimulation parameters must be identified for effective treatment.