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Environment-Induced Protection Against Dementia Could Be Heritable, Suggests Mouse Study

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An LSU Health New Orleans research team working in a mouse model of vascular cognitive impairment (VCI) has found that repetitive exposure to environmental hypoxia (air with lower-than-normal oxygen content) prevented memory loss.

They also demonstrated for the first time that offspring can inherit this protection against dementia. Results of the study led by Jeff Gidday, PhD, Professor of Ophthalmology, Biochemistry, Neuroscience, and Physiology, are published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, available here.

“As with Alzheimer’s, the molecular mechanisms that cause vascular dementia are complex, and efficacious therapies are still lacking,” notes Dr. Gidday.

The researchers tested the hypothesis that epigenetics – changes in behavior and environment that trigger changes in the way genes are turned on and off -- may provide resilience to VCI.

“We also tested the hypothesis that this epigenetic treatment modifies germ cells (eggs and sperm) so that the adult offspring of the animals receiving this therapy prior to mating would inherit VCI resilience, in the absence of direct treatment,” Dr. Gidday adds.

The scientists found that their physiologic stimulus – repetitive exposures of the mice to environmental hypoxia – air with low oxygen content akin to what we experience at high altitude – for one hour per day, three times per week over two consecutive months, prevented loss of recognition memory and reversed impairments in nerve-to-nerve communication in the hippocampus, a key brain region involved in memory consolidation. They also documented the same resilience to memory impairment in adult offspring of a separate group of mice exposed to repetitive hypoxia prior to mating – an inter-generational epigenetic response.

Vascular cognitive impairment is the second leading cause of dementia. According to the National Institutes of Health, it is caused by different conditions that interrupt the flow of blood and oxygen supply to the brain and damage blood vessels in the brain. These can include prior strokes that can be small and without noticeable symptoms. Other abnormalities commonly seen in the brains of people with vascular dementia are diseased small blood vessels and changes in “white matter” — the connecting “wires” of the brain that are critical for relaying messages between brain regions.

The study also showed that their “adaptive epigenetics” treatment protected against the loss of white matter, another human-like feature of the mouse dementia model.

“These results demonstrate that epigenetic therapies may hold promise for preventing memory loss and other manifestations of dementia, and that, remarkably, the disease resilience so induced by these therapies may also be heritable by first-generation offspring,” Dr. Gidday concludes.

Other members of the LSU Health New Orleans research team included recent Physiology graduate Krystal Courtney D. Belmonte, PhD; Cell Biology & Anatomy graduate student Eleanor B. Holmgren; and Tiffany Wills, PhD, Assistant Professor of Cell Biology & Anatomy.

Reference: Belmonte KCD, Holmgren EB, Wills TA, Gidday JM. Epigenetic conditioning induces intergenerational resilience to dementia in a mouse model of vascular cognitive impairment. Alzheimer’s & Dementia. n/a(n/a). doi:10.1002/alz.12616

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