Could hypoxia build resilience against dementia?

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An intriguing new study reveals that, in mice, repeated exposure to hypoxia can protect against dementia. Manu Prats/Stocksy
  • A recent study using a mouse model of vascular cognitive impairment found that repeated exposure to low oxygen levels prevented memory loss.
  • Under controlled conditions, oxygen deprivation can slow neurological degeneration and decrease and promote increased cerebral blood flow.
  • These seemingly paradoxical results suggest that changing behaviors and environments may influence future therapies in the treatment of Alzheimer’s disease and other neurocognitive diseases.

Vascular dementia is the second leading cause of dementia after Alzheimer’s disease. This happens due to the interruption of blood and oxygen supply to the brain, which damages the blood vessels.

Low oxygen levels elsewhere in the body can also disrupt other critical organs and their functions. For example, reduced blood supply to the heart can lead to cardiovascular disease and heart attacks.

Since low levels of oxygen in the body can cause life-threatening conditions, it seems paradoxical to deprive a tissue or organ of oxygen to confer benefits. However, a group of researchers are looking at some potential benefits of exposure to low levels of oxygen, also known as hypoxia.

Scientists recently conducted a study to answer two hypotheses:

  1. This hypoxia will reduce deficits in a mouse model of vascular cognitive impairment and dementia.
  2. JSubsequent generations will inherit this “dementia resistant phenotype”.

The results of the study are in Alzheimer’s and dementia: the journal of the Alzheimer’s Association.

Although the genetic code we are born with remains constant throughout our lives, the way this code can be read or translated can change. This is called epigenetics. Our environment and our behaviors can influence not what the DNA code “says”, but whether or not a gene is turned on or “off”.

For example, methylation is a form of epigenetic change. Certain behaviors can cause sections of DNA to be methylated, which means that a methyl group is added to the DNA.

Once a gene is methylated, it is less likely to be expressed. So, although the gene is still present and functional, it is effectively disabled or reduced.

Importantly, these epigenetic changes can pass from generation to generation without altering the genetic code.

In the current study, the scientists subjected the experimental animals to repetitive hypoxic conditioning (RHC). Animals in the RHC condition experienced low oxygen levels – similar to those at high altitude – for 1 hour every other day over a 2 month period.

After this conditioning, the researchers subjected the mice to chronic cerebral hypoperfusion, which induces vascular dementia.

They assessed changes in memory and other brain functions 3 and 4 months later, respectively.

Research found that induced deficits in memory and brain function caused by chronic cerebral hypoperfusion were reversed in animals that had undergone CHR.

Similarly, the offspring of parents treated with CHR also showed strong resilience to dementia without experiencing CHR.

The authors write:[N]either mice treated directly with 2 months of RHC or their adult offspring showed changes in white matter myelin density, neurocognitive function, or synaptic plasticity.

Although there have been few studies investigating the potential health benefits of hypoxia, the authors outline some theories as to why it might work.

One such theory is that hypoxia induces angiogenesis, which is the development of new blood vessels. This, the authors explain, could improve cerebral blood flow.

They also explain that “[r]resilience can also be provided by direct pro-survival adaptations that RHC induces in cells of the neurovascular unit, making them more resistant to the pathological consequences of [vascular dementia].”

Older studies have focused on an experimental procedure called Remote limb ischemic conditioning (RLIC). In RLIC, brief reversible periods of oxygen deprivation are followed by area reperfusion or oxygen replenishment. This gradual process makes target tissues and organs resistant to damage caused by ischemia.

Medical News Today spoke with the study’s corresponding author, Jeff M. Gidday, Ph.D., professor of ophthalmology, biochemistry, neurosciences, physiology and molecular biology at the Louisiana State University Health Sciences Center in the New Orleans.

“Dr. David Hess’ lab at the University of Augusta in Georgia had previously shown that a different epigenetic stimulus – [RLIC] – protected against memory loss in the same animal model of vascular dementia,” he explained.

“RLIC is considered a non-harmful approach to inducing beneficial epigenetic responses in humans that can mimic what we elicited using intermittent hypoxia in mice or vice versa. The ideal ‘dose’ of RLIC can still require elucidation, depending on an individual’s gender, age, and other comorbidities, but in principle this is an “adaptive epigenetics” therapeutic approach that many believe still holds great promise on the clinical plan.

“Phone [intragenerational] epigenetic (single generation) or transgenerational (multiple generations) effects are not new, but 99% of studies in these disciplines […] focus on how repetitive undesirable stress causes or contributes to the cause of disease in future generations,” Dr. Gidday continued.

According to the authors of the new study, the vast majority of epigenetics research has so far focused on “negative” outcomes. In other words, they attempted to identify epigenetic changes that produce negative consequences in offspring. The authors write:

“[O]Our findings are the first to document the inheritance of an epigenetically induced phenotype that protects against disease.

“We believe that germ cell changes (again, plasticity) are really a 50-50 scenario, which means both negative and beneficial outcomes can result depending on the nature of the epigenetic stimulus – we just showed that it was indeed possible,” Dr Gidday said. DTM.

Speaking of the limitations of the study, Dr Gidday said: “In terms of our cross-generational results, these are not suitable for clinical testing per se, which would take decades, but they do suggest that all sorts of behaviors of healthy lives before conception can promote disease. resilience in our children and grandchildren that we may not even be aware of. Of course, the reverse is also true.

“Although our treatment was effective,” he continued, “we did not use older mice or mice with common comorbidities like hypertension, which would better reflect the human population that develops dementia.” .

“It would also be wise for other laboratories to repeat our studies with an extended battery of tests to better understand the different types of memory. — and learning, and other cognitive functions – that our treatment can abrogate in vascular dementia and in other preclinical models of dementia, including, most obviously, Alzheimer’s disease.

DTM also spoke with Dr. Davey Smith, MS, FACP, Vice Chairman of the Department of Medicine at the University of California San Diego at La Jolla. He concluded :

“I think this is a fascinating study further showing that epigenetic changes can be inherited and influence health. In this mouse model, researchers show the link between epigenetic changes and resilience to dementia These new data could pave the way for new therapies aimed at epigenetics for the treatment of dementia.Of course, mice are not people, so human studies will be needed.

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