Photos from the analysis paper present a rise in neurogenesis (as indicated by two markers: Ki67 and EdU) in mice uncovered to 40Hz stimulation in comparison with these uncovered solely to ambient mild and sound. Yellow arrows spotlight cases of the markers. Credit score: Alana Down Syndrome Middle at MIT
Research by a rising variety of labs have recognized neurological well being advantages from exposing human volunteers or animal fashions to mild, sound and/or tactile stimulation on the mind’s “gamma” frequency rhythm of 40Hz. Within the newest such analysis at The Picower Institute for Studying and Reminiscence and Alana Down Syndrome Middle at MIT, scientists discovered that 40Hz sensory stimulation improved cognition and circuit connectivity and inspired the expansion of recent neurons in mice genetically engineered to mannequin Down syndrome.
Li-Huei Tsai, Picower Professor at MIT and senior writer of the brand new examine in PLOS ONE, mentioned that the outcomes are encouraging but additionally cautioned that rather more work is required to check whether or not the tactic, referred to as GENUS (for Gamma Entrainment Utilizing Sensory Stimulation), might present scientific advantages for folks with Down syndrome. Her lab has begun a small examine with human volunteers at MIT.
“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,” mentioned Tsai, who directs The Picower Institute and The Alana Middle, and is a member of MIT’s Mind and Cognitive Sciences college.
Nonetheless, she mentioned, the newly printed article provides proof that GENUS can promote a broad-based, restorative, “homeostatic” well being response within the mind amid all kinds of pathologies. Most GENUS research have addressed Alzheimer’s illness in people or mice, however others have discovered advantages from the stimulation for circumstances similar to “chemo brain,” and stroke.
A “reel” describing a brand new examine by MIT researchers discovering advantages in Down syndrome mouse fashions from 40Hz sensory stimulation. Credit score: Alana Down Syndrome Middle at MIT
Down syndrome advantages
Within the examine, the analysis crew led by postdoc Md Rezaul Islam and former graduate scholar Brennan Jackson labored with the generally used “Ts65Dn” Down syndrome mouse mannequin. The mannequin recapitulates key points of the dysfunction, although it doesn’t precisely mirror the human situation, which is brought on by carrying an additional copy of chromosome 21.
Within the first set of experiments within the paper, the crew exhibits that an hour a day of 40Hz mild and sound publicity for 3 weeks was related to important enhancements on three customary short-term reminiscence assessments—two involving distinguishing novelty from familiarity and one involving spatial navigation.
As a result of these sorts of reminiscence duties contain a mind area referred to as the hippocampus, the researchers checked out neural exercise there and measured a major improve in exercise indicators amongst mice that obtained the GENUS stimulation vs. people who didn’t.
To higher perceive how stimulated mice might present improved cognition, the researchers examined whether or not cells within the hippocampus modified how they specific their genes. To do that, the crew used a way referred to as single cell RNA sequencing, which supplied a readout of how practically 16,000 particular person neurons and different cells transcribed their DNA into RNA, a key step in gene expression.
Most of the genes whose expression diversified most prominently in neurons between the mice that obtained stimulation and people who didn’t have been straight associated to forming and organizing neural circuit connections referred to as synapses.
To verify the importance of that discovering, the researchers straight examined the hippocampus in stimulated and management mice. They discovered that in a essential subregion, the dentate gyrus, stimulated mice had considerably extra synapses.
Diving deeper
The crew not solely examined gene expression throughout particular person cells, but additionally analyzed that information to evaluate whether or not there have been patterns of coordination throughout a number of genes. Certainly, they discovered a number of such “modules” of co-expression. A few of this proof additional substantiated the concept 40Hz-stimulated mice made vital enhancements in synaptic connectivity, however one other key discovering highlighted a job for TCF4, a key regulator of gene transcription wanted for producing new neurons, or “neurogenesis.”
The crew’s evaluation of genetic information advised that TCF4 is underexpressed in Down syndrome mice however the researchers noticed improved TCF4 expression in GENUS-stimulated mice. When the researchers went to the lab bench to find out whether or not the mice additionally exhibited a distinction in neurogenesis, they discovered direct proof that stimulated mice exhibited greater than unstimulated mice within the dentate gyrus.
These will increase in TCF4 expression and neurogenesis are solely correlational, the researchers famous, however they hypothesize that the rise in new neurons seemingly helps clarify at the very least among the improve in new synapses and improved brief time period reminiscence operate.
“The increased putative functional synapses in the dentate gyrus is likely related to the increased adult neurogenesis observed in the Down syndrome mice following GENUS treatment,” Islam mentioned.
This examine is the primary to doc that GENUS is related to elevated neurogenesis.
The evaluation of gene expression modules additionally yielded different key insights. One is {that a} cluster of genes whose expression usually declines with regular getting older and in Alzheimer’s illness, remained at increased expression ranges amongst mice who obtained 40Hz sensory stimulation.
And the researchers additionally discovered proof that mice that obtained stimulation retained extra cells within the hippocampus that specific Reelin. Reelin-expressing neurons are particularly susceptible in Alzheimer’s illness, however expression of the protein is related to cognitive resilience amid Alzheimer’s illness pathology, which Ts65Dn mice develop. About 90% of individuals with Down syndrome develop Alzheimer’s illness, usually after the age of 40.
“In this study, we found that GENUS enhances the percentage of Reln+ neurons in hippocampus of a mouse model of Down syndrome, suggesting that GENUS may promote cognitive resilience,” Islam mentioned.
Taken along with different research, Tsai and Islam mentioned, the brand new outcomes add proof that GENUS helps to stimulate the mind on the mobile and molecular stage to mount a homeostatic response to aberrations brought on by illness pathology, be it neurodegeneration in Alzheimer’s, demyelination in chemo mind, or deficits of neurogenesis in Down syndrome.
However the authors additionally cautioned that the examine had limits. Not solely is the Ts65Dn mannequin an imperfect reflection of human Down syndrome, but additionally the mice used have been all male. Furthermore, the cognitive assessments within the examine solely measured short-term reminiscence. And at last, whereas the examine was novel for extensively inspecting gene expression within the hippocampus amid GENUS stimulation, it didn’t have a look at modifications in different cognitively essential mind areas such because the prefrontal cortex.
Along with Jackson, Islam and Tsai, the paper’s different authors are Maeesha Tasnim Naomi, Brooke Schatz, Noah Tan, Mitchell Murdock, Dong Shin Park, Daniela Rodrigues Amorim, Fred Jiang, S. Sebastian Pineda, Chinnakkaruppan Adaikkan, Vanesa Fernandez, Ute Geigenmuller, Rosalind Mott Firenze, Manolis Kellis and Ed Boyden.
Extra info:
Md Rezaul Islam et al, Multisensory gamma stimulation enhances grownup neurogenesis and improves cognitive operate in male mice with Down Syndrome, PLOS One (2025). DOI: 10.1371/journal.pone.0317428
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In Down syndrome mice, 40Hz mild and sound enhance cognition, neurogenesis and connectivity (2025, April 25)
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