Gamma-patterned sensory stimulation reverses synaptic plasticity
deficits in rat models of early Alzheimer's disease
Abstract
Non-invasive sensory stimulation in the range of the brain’s gamma
rhythm (30-100 Hz) is emerging as a new potential therapeutic strategy
for the treatment of Alzheimer’s disease (AD). Here we investigated the
effect of repeated combined exposure to 40 Hz synchronized sound and
light stimuli on hippocampal long-term potentiation (LTP) in vivo in
three rat models of early AD. We employed a very complete model of AD
amyloidosis, amyloid precursor protein (APP)-overexpressing transgenic
McGill-R-Thy1-APP rats at an early pre-plaque stage, systemic treatment
of transgenic APP rats with corticosterone modelling certain
environmental AD risk factors and, importantly, intracerebral injection
of highly disease-relevant AD patient-derived synaptotoxic beta-amyloid
and tau in wild-type animals. We found that daily sessions of 40 Hz
sensory stimulation fully abrogated the inhibition of LTP in all three
models. Moreover, there was a negative correlation between the magnitude
of LTP and the level of active caspase-1 in the hippocampus of
transgenic APP animals which suggests that the beneficial effect of 40
Hz stimulation was dependent on modulation of pro-inflammatory
mechanisms. Our findings support ongoing clinical trials of
gamma-patterned sensory stimulation in early AD.