Nonharmful stress protects against disease in offspring

Date:
September 10, 2020
Source:
Louisiana State University Health Sciences Center
Summary:
Researchers report what is believed to be the first study in a
mammalian model documenting the reprogramming of heritability to
promote disease resilience in the next generation.



FULL STORY ========================================================================== Research led by Jeff Gidday, PhD, Professor of Ophthalmology,
Biochemistry, Neuroscience, and Physiology at LSU Health New Orleans
School of Medicine, reports what is believed to be the first study in a mammalian model documenting the reprogramming of heritability to promote disease resilience in the next generation. The results are published in
the Journal of Investigative Ophthalmology & Visual Sciences, the flagship journal of the Association for Research in Vision and Ophthalmology
(ARVO), available here.


==========================================================================
The researchers used a functional measurement to document resilience to
injury of the retina of adult mice that were born to parents who were
exposed to intermittent, mild systemic hypoxia (reduced concentrations
of oxygen) for several months prior to mating, even though the
injury-protected mice received no treatment themselves. The therapy,
akin to brief exposures to high-altitude air, is considered "epigenetic" because it modifies which genes are converted into proteins in tissues throughout the body, including germ cells (sperm and eggs).

"We exposed mice to nonharmful hypoxia to trigger these adaptive changes"
says first-author Jarrod Harman, a doctoral student in Dr. Gidday's
lab. "But there are many epigenetic stimuli that could cause these
changes as well, including exercise, and other 'positive' stressors. Not
all stress is bad for you." The researchers also extensively analyzed
the injury-resilient retinae. By comparing the protein profiles of
these retinae to those of mice derived from untreated parents using
mass spectrometry, they identified many of the potential proteins
and related biochemical mechanisms by which this intergenerational, injury-resilient state is achieved. These proteins, serving in both
functional and structural roles, represent potential therapeutic targets
for drug development to protect against retinal diseases associated with
an inadequate blood supply (ischemic retinopathies).

Other studies have shown that repetitive exposure to adverse stimuli can enhance the susceptibility of first-generation offspring to disease. But
Gidday contends that, conversely, this is the first study to use a mild, nonharmful stress like intermittent systemic hypoxia to provide protection against disease in first-generation offspring.

"Research has shown that environmental enrichment can enhance some
baseline memory metrics in both parents and offspring," Gidday says, "but
no study has ever shown that offspring can inherit a neuroprotective
phenotype induced in parents by epigenetics. The implications of
this finding with respect to our understanding of the heritability of
disease susceptibility, and disease resilience, is profound." Companion studies addressing the safety profile of the treatment showed that the intermittently reduced oxygen stimulus used to trigger injury resilience
across generations caused no injury to the most oxygen-sensitive cells
of the brains of mice receiving the treatment, nor affected the normal structure or function of the retina of the adult offspring derived from
treated mice.

Ischemic retinopathies are diseases that result from some degree of
prolonged, lower-than-normal blood flow to the retina, compromising the delivery of much- needed oxygen and glucose to this very metabolically
active tissue. The most well-known examples are glaucoma and diabetic retinopathy, but the retina can also be deprived of blood flow acutely, as happens with a heart attack or stroke. Collectively, the resultant visual impairment suffered by those with these retinopathies is staggering,
and in a large percentage of cases, complete blindness can ensue.

"The direct inheritance of an induced phenotype is what Lamarck famously proposed in 1809, the year Darwin was born" says Gidday. "Here we are,
almost 200 years later, finding evidence to support this concept,
despite it being largely displaced for the last 150 years by Darwin's
Theory of Natural Selection. More than likely both operate under
distinct environmental situations to enhance both short- and long-term reproductive fitness." The research was supported by grants from the
National Eye Institute of the National

========================================================================== Story Source: Materials provided by Louisiana_State_University_Health_Sciences_Center. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Jarrod C. Harman, Jessie J. Guidry, Jeffrey M. Gidday. Intermittent
Hypoxia Promotes Functional Neuroprotection from Retinal Ischemia
in Untreated First-Generation Offspring: Proteomic Mechanistic
Insights.

Investigative Opthalmology & Visual Science, 2020; 61 (11): 15 DOI:
10.1167/iovs.61.11.15 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200910150237.htm

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