Summary: New research has demonstrated that 40Hz sensory stimulation ( GENUS) in mice modeling Down syndrome enhances memory, increases brain circuit connectivity, and encourages the growth of new neurons. In the study, regular light and sound publicity boosted achievement in remembrance tasks and promoted protein activity linked to neural development.
Additionally, researchers discovered that more genes are expressed that prevent aging and Alzheimer ‘s-like degeneration. Although promising, more research is required to establish whether identical advantages can be had in people.
Important Information:
- Memory Enhancement: 40Hz tactile stimulation improved Down syndrome rat types ‘ ability to retain their short-term memory.
- Increased New Neuron Growth and Synaptic Connectivity in the Hippocampus: Stimulated mice demonstrated increased nerve growth and neuronal communication.
- Alzheimer’s Link: Activation helped protect neurons linked to cognitive endurance against Alzheimer’s disease.
Origin: MIT Picower Institute
A growing body of scientific research has found that exposure to human participants or animal designs to light, sound, and/or sensory stimulation at the brain’s “gamma” speed pattern of 40Hz has a beneficial effect on neurological health.
In the latest for analysis at The Picower Institute for Learning and Memory and , Alana Down Syndrome Center at MIT, researchers found that 40Hz tactile stimulation improved thinking and loop communication and encouraged the growth of new cells in mice genetically engineered to design Down syndrome.
The results are encouraging, but Li-Huei Tsai, Picower Professor at MIT and senior author of the new study in , PLOS ONE, cautioned that much more research is needed to determine whether the method, called GENUS ( for Gamma Entrainment Using Sensory Stimulation ), could be effective in treating people with Down syndrome.
Her test has begun a , smaller research  , with human volunteers at MIT.
We need to be careful because there isn’t but any data to show whether GENUS’s use of an inadequate rat model on Down syndrome also applies to humans, said Tsai, who directs The Picower Institute and The Alana Center and is a member of MIT’s Brain and Cognitive Sciences university.
The recently published article, she said, adds further evidence that GENUS you market a broad-based, therapeutic, “homeostatic” health response in the brain in the presence of a range of pathologies.
Most , GENUS studies , have addressed Alzheimer’s disease in people or animals, but others have found gains from the excitement for conditions like as” treatment mind”, and , injury.
Benefits of Down syndrome
The research team, which was led by postdoc Md Rezaul Islam and former graduate student Brennan Jackson, used the popular” Ts65Dn” Down syndrome mouse model for the study.
The model recapitulates key aspects of the disorder, though it does not exactly mirror the human condition, which is caused by carrying an extra copy of chromosome 21.
The team’s initial set of experiments in the paper demonstrate that 40Hz light and sound exposure for three weeks, which included two that involved distinguishing novelty from familiarity and one that involved spatial navigation, had significant effects on three standard short-term memory tests.
The researchers examined the hippocampus and found that mice that received GENUS stimulation had significantly increased activity indicators there because these kinds of memory tasks involve a brain region.
To better understand how stimulated mice could show improved cognition, the researchers examined whether cells in the hippocampus changed how they express their genes.
The team used a method known as single cell RNA sequencing to obtain a readout of how nearly 16, 000 individual neurons and other cells transcribed their DNA, a crucial step in gene expression, into RNA.
Many of the genes involved in the generation and organization of neural circuit connections called synapses had direct connections to the neurons that received stimulation, and those that did not.
To confirm the significance of that finding, the researchers directly examined the hippocampus in stimulated and control mice. They discovered that stimulated mice had significantly more synapses in a critical subregion, the dentate gyrus.
delve deeper
The team not only examined gene expression across individual cells, but also analyzed that data to assess whether there were patterns of coordination across multiple genes. In fact, they discovered a number of such “modules” of co-expression.
Another important finding highlighted a role for TCF4, a key regulator of gene transcription required for the generation of new neurons, or “neurogenesis,” in the development of the hypothesis that 40Hz-stimulated mice significantly improved synaptic connectivity.  ,
The team’s analysis of genetic data revealed that Down syndrome mice had an underexpressed TCF4, but they also discovered that GENUS-stimulated mice had increased TCF4 expression.
When the researchers examined the lab bench to determine whether the mice also had different neurogenesises, they discovered direct evidence that stimulated mice had more of an effect on the dentate gyrus than unstimulated mice.
These increases in TCF4 expression and neurogenesis are only correlational, the researchers noted, but they hypothesize that the increase in new neurons likely helps explain at least some of the increase in new synapses and improved short term memory function.
Islam claimed that the increased putative functional synapses in the dentate gyrus is likely related to the GENUS treatment-related increase in adult neurogenesis.
This study is the first to demonstrate that increased neurogenesis is related to GENUS.
The analysis of gene expression modules also yielded other key insights. One of the findings was that mice who were given 40Hz sensory stimulation had higher expression levels in a group of genes whose expression typically decreased with normal aging and Alzheimer’s disease.
Additionally, the researchers discovered proof that stimulation-retained mice retained more hippocampus cells that express Reelin. Reelin-expressing neurons are especially vulnerable in Alzheimer’s disease, but expression of the protein is associated with cognitive resilience amid Alzheimer’s disease pathology, which Ts65Dn mice develop. Alzheimer’s disease typically develops after the age of 40 in about 90 % of Down syndrome sufferers.
According to Islam,” We found that GENUS increases the percentage of Reln + neurons in a mouse model of Down syndrome,” which suggests that GENUS may promote cognitive resilience.
Taken together with other studies, Tsai and Islam said, the new results add evidence that GENUS helps to stimulate the brain at the cellular and molecular level to mount a homeostatic response to aberrations caused by disease pathology, be it neurodegeneration in Alzheimer’s, demyelination in chemo brain, or deficits of neurogenesis in Down syndrome.
The study had limitations, the authors warned, but they also raised caution. The Ts65Dn model is an imperfect reflection of human Down syndrome, and the mice used were all male. Moreover, the cognitive tests in the study only measured short-term memory.
Finally, despite being novel in its extensive investigation of gene expression in the hippocampus during GENUS stimulation, the study did not examine changes in other highly cognizant brain regions, such as the prefrontal cortex.
The paper’s other 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, in addition to Jackson,
Funding for the study came from the Alana Down Syndrome Center at MIT and the Alana USA Foundation, the National Science Foundation, the “la Caixa” Banking Foundation, an EMBO long term postdoctoral fellowship, Barbara J. Weedon, Henry E. Singleton, and the Hubolow family.
About this news about Down syndrome and brain stimulation
Author: David Orenstein
Source: Picower Institute at MIT
Contact: David Orenstein – Picower Institute at MIT
Image: The image is credited to Neuroscience News
Original Research: Open access.
Li-Huei Tsai and colleagues ‘ study” Multisensory gamma stimulation enhances adult neurogenesis and improves cognitive function in male mice with Down syndrome.” PLOS One
Abstract
Multisensory gamma stimulation enhances adult neurogenesis and improves cognitive function in male mice with Down Syndrome
Down syndrome ( DS ) has been linked to hippocampus-related impaired neurogenesis and abnormal synaptic functions. These changes are in line with the memory and other cognitive deficits that people with DS have reported.
Additionally, a recent study found dementia to be associated with mortality in 70 % of older adults with DS.
However, there are only a few therapeutic options left to manage cognitive performance in those with DS.
We have previously demonstrated the efficacy of using gamma-frequency sensory stimulation to treat cognitive decline in both mouse and human subjects.
The sensory gamma stimulation reduced Alzheimer’s disease ( AD ) related pathology, improved neuronal survival and synaptic density, and enhanced cognitive function in multiple mouse models of AD.
We demonstrated that the reduced pathology was present in 40 Hz stimulation but not at 8 or 80 Hz stimulation, according to more recent literature.
Other researchers have also documented the beneficial effects of gamma stimulation in AD as well as in other neurological conditions like Parkinson’s.
However, the efficacy of sensory gamma stimulation at 40Hz has not been tested in DS.
The most popular DS model, the Ts65Dn mouse, has an extra chromosome that extends most of the distal region of chromosome 16 homologous to human chromosome 21.
This murine model recapitulates phenotypes associated with DS, including hippocampal-dependent spatial learning and memory deficits and synaptic abnormalities.
As such, this murine model provides invaluable opportunities for exploring and testing potential therapeutic interventions for cognitive deficits in DS.
We tested the effects of sensory gamma stimulation on cognitive benefits of the well-known DS mouse model, finding that it improved adult neurogenesis, increased cognitive function, and caused expression changes in genes involved in synaptic organization using this well-developed DS mouse model.
