Researchers use 40Hz pulses to ‘hack’ cognitive deficits in Down syndrome mice

As advances in neuroscience continue, researchers have managed to deploy an innovative method to encourage the growth of new neurons in mice genetically engineered to model Down syndrome, improving cognition and synapse connectivity.

Indeed, the scientists at The Picower Institute for Learning and Memory and Alana Down Syndrome Center at the Massachusetts Institute of Technology have discovered that 40Hz sensory stimulation provided multiple neurological health benefits in a mouse model, according to a study published on April 24.

Specifically, the research team led by postdoc Md Rezaul Islam and former graduate student Brennan Jackson worked with the commonly used ‘Ts65Dn’ Down syndrome mouse model, exposing the mice to 40Hz of light and sound pulses an hour a day for three weeks using the GENUS (Gamma Entrainment Using Sensory Stimulation) method.

‘Hacking’ Down syndrome cognitive deficits

As it happens, the results were significant, with the scientists observing substantial improvements in three standard short-term memory tests involving a brain region called the hippocampus and recording a considerable increase in activity indicators among mice that received the stimulation as opposed to those that did not.

To better understand this outcome, they analyzed whether cells in the hippocampus changed how they express their genes using single-cell RNA sequencing and found that many of the genes whose expression varied most prominently in neurons between the two mice groups were directly related to forming and organizing synapses.

Furthermore, they also discovered a role for TCF4, a key regulator of gene transcription needed for generating new neurons, or ‘neurogenesis,’ suggesting its underexpression in Down syndrome, and the GENUS-stimulated mice witnessed improved TCF4 expression or increased neurogenesis.

Additionally, the scientists found evidence that the GENUS-stimulated mice retained more cells in the hippocampus that express Reelin, usually particularly vulnerable in Alzheimer’s disease (that 90% of people with Down syndrome develop), demonstrating better cognitive resilience amid the disease pathology.

Commenting on the breakthrough, Li-Huei Tsai, Picower Professor at MIT and senior author of the study, pointed out that there should be more tests carried out in humans in order to verify the method’s clinical efficiency in people with Down syndrome:

“While this work, for the first time, shows the beneficial effects of GENUS on Down syndrome using an imperfect mouse model, we need to be cautious as there is not yet data showing whether this also works in humans.”

Nonetheless, these findings have proven that GENUS can promote a broad-based, restorative, ‘homeostatic’ health response in the brain in a range of pathologies, also including Alzheimer’s disease, stroke, and the so-called ‘chemo brain.’