Repressor element-1 silencing transcription factor (REST)-dependent epigenetic remodeling is critical to ischemia-induced neuronal death

I got nothing out of this so your doctor can contact the two given email addresses to see what needs to be done to followup research in humans and create a stroke protocol for this. No followup, they need to be fired. Dead wood needs to be removed.  

Repressor element-1 silencing transcription factor (REST)-dependent epigenetic remodeling is critical to ischemia-induced neuronal death

Kyung-Min Noh, Jee-Yeon Hwang, Antonia Follenzi, Rodoniki Athanasiadou, Takahiro Miyawaki, John M. Greally, Michael V. L. Bennett, and R. Suzanne Zukin

PNAS February 27, 2012. 201121568; published ahead of print February 27, 2012. https://doi.org/10.1073/pnas.1121568109

1. Contributed by Michael V. L. Bennett, January 15, 2012 (sent for review December 22, 2011)

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Abstract

Dysregulation of the transcriptional repressor element-1 silencing transcription factor (REST)/neuron-restrictive silencer factor is important in a broad range of diseases, including cancer, diabetes, and heart disease. The role of REST-dependent epigenetic modifications in neurodegeneration is less clear. Here, we show that neuronal insults trigger activation of REST and CoREST in a clinically relevant model of ischemic stroke and that REST binds a subset of “transcriptionally responsive” genes (gria2, grin1, chrnb2, nefh, nfκb2, trpv1, chrm4, and syt6), of which the AMPA receptor subunit GluA2 is a top hit. Genes with enriched REST exhibited decreased mRNA and protein. We further show that REST assembles with CoREST, mSin3A, histone deacetylases 1 and 2, histone methyl-transferase G9a, and methyl CpG binding protein 2 at the promoters of target genes, where it orchestrates epigenetic remodeling and gene silencing. RNAi-mediated depletion of REST or administration of dominant-negative REST delivered directly into the hippocampus in vivo prevents epigenetic modifications, restores gene expression, and rescues hippocampal neurons. These findings document a causal role for REST-dependent epigenetic remodeling in the neurodegeneration associated with ischemic stroke and identify unique therapeutic targets for the amelioration of hippocampal injury and cognitive deficits.

• chromatin remodeling
• global ischemia
• CA1
• synaptic plasticity

Footnotes

• ↵¹K.-M.N. and J.-Y.H. contributed equally to this work.
• ↵²To whom correspondence may be addressed. E-mail: michael.bennett@einstein.yu.edu or suzanne.zukin@einstein.yu.edu.

First-of-Its-Kind Study Explains Why Rest is Critical After A Concussion

How much rest should you have after a stroke? Doctors and researchers keep pushing ASAP. Is that correct or not? We'll never know because we have NO fucking leadership or strategy in stroke. The boards of directors of our stroke associations are completely failing at giving requirements to their presidents. 'Solve all the problems in stroke, We don't care how BHAGs they are'. Based on these articles which way does your doctor fall? If we had stroke protocols we could put in pros/cons and add new information as needed. But we don't. Your children and grandchildren will be screwed also if we don't replace all the existing stroke leadership with competent survivors.

People With Brain Injuries Heal Faster If They Get Up And Get Moving 

When should rehabilitation begin after stroke? 

Early Stroke Rehab Helps But Raises Fall Risk 

late start to stroke therapy ok

 

First-of-Its-Kind Study Explains Why Rest is Critical After A Concussion

WASHINGTON — Doctors who order several days of rest after a person suffers a concussion are giving sound advice, say researchers, and new data from animal models explains why.  
Georgetown University Medical Center neuroscientists say rest — for more than a day — is critical for allowing the brain to reset neural networks and repair any short-term injury. The new study in mice also shows that repeated mild concussions with only a day to recover between injuries leads to mounting damage and brain inflammation that remains evident a year after injury.
“It is good news that the brain can recover from a hit if given enough time to rest and recover. But on the flip side, we find that the brain does not undertake this rebalancing when impacts come too close together,” says the study’s lead researcher, Mark P. Burns, PhD, assistant professor of neuroscience at GUMC and director of the Laboratory for Brain Injury and Dementia.
This first-of-its-kind study, published in the March 2016 issue of American Journal of Pathology, modeled repeated mild head trauma as a means to investigate brain damage that occurs after a sports, military or domestic abuse injury.
Investigators developed a mouse model of repetitive, extremely mild concussive impacts conducted while the mouse is anesthetized. They compared the brain’s response to a single concussion with an injury received daily for 30 days and one received weekly over 30 weeks.
Mice with a single insult temporarily lose 10-15 percent of the neuronal connections in their brains, but no inflammation or cell death resulted, Burns says. With three days rest, all neuronal connections were restored. This neuronal response is not seen in mice with daily concussions, but the pattern is restored when a week of rest is given between each insult, Burns says.
When a mild concussion occurred each day for a month, inflammation and damage to the brain’s white matter resulted. “This damage became progressively worse for two months and remained apparent one year after the last impact,” Burns says.
“The findings mirror what has been observed about such damage in humans years after a brain injury, especially among athletes,” Burns says. “Studies have shown that almost all people with single concussions spontaneously recover, but athletes who play contact sports are much more susceptible to lasting brain damage. These findings help fill in the picture of how and when concussions and mild head trauma can lead to sustained brain damage.”
Georgetown co-authors are first author Charisse N. Winston, PhD, Maia Parsadanian, David N. Zapple, Sonia Villapol, PhD, and undergraduate students David Barton, Tiffany E. Wilkins, Aidan Neustadtl, Deepa Chellappa, and Andrew D. Alikhani. Contributors also include Emmanuel Planel, PhD, and Anastasia Noel, PhD, from the Centre Hospitalier de l'Université Laval, Neurosciences, Québec, Canada.
The study was supported by Georgetown University’s Neural Injury and Plasticity Training Program, the National Institute for Neurological Disorders and Stroke (R01 NS067417), a supplement to Promote Diversity in Health-Related Research, a donation from KPB Corporation, the Canadian Institute of Health Research, Fonds de Recherche en Santé du Québec and the Natural Sciences and Engineering Research Council of Canada.

Protein May Hold the Key to Who Gets Alzheimer’s

The answer to this may explain why nun Bernadette could function so well.
http://www.nytimes.com/2014/03/20/health/fetal-gene-may-protect-brain-from-alzheimers-study-finds.html?

It is one of the big scientific mysteries of Alzheimer’s disease: Why do some people whose brains accumulate the plaques and tangles so strongly associated with Alzheimer’s not develop the disease?

Now, a series of studies by Harvard scientists suggests a possible answer, one that could lead to new treatments if confirmed by other research.

The memory and thinking problems of Alzheimer’s disease and other dementias, which affect an estimated seven million Americans, may be related to a failure in the brain’s stress response system, the new research suggests. If this system is working well, it can protect the brain from abnormal Alzheimer’s proteins; if it gets derailed, critical areas of the brain start degenerating.

The rest is at the link behind  the NYTimes paywall.

Abstract here;

REST and stress resistance in aging and Alzheimer’s disease

Article preview View full access options

• Tao Lu,
• Liviu Aron,
• Joseph Zullo,
• Ying Pan,
• Haeyoung Kim,
• Yiwen Chen,
• Tun-Hsiang Yang,
• Hyun-Min Kim,
• Derek Drake,
• X. Shirley Liu,
• David A. Bennett,
• Monica P. Colaiácovo
• & Bruce A. Yankner

• Affiliations
• Contributions
• Corresponding author

Nature

(2014)

doi:10.1038/nature13163

Received

27 June 2013

Accepted

21 February 2014

Published online

19 March 2014

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Abstract

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Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer’s disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer’s disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid β-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer’s disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain.

What is your doctor doing to make sure your 33% chance of getting dementia/Alzheimers post stroke is avoided?

 

 

Genetic ablation of Rest leads to in vitro-specific derepression of neuronal genes during neurogen of neuronal genes during neurogenesis

Too bad I'm not a new graduate student. Dozens and dozens of possibilities to look into.
Who is leading the drive to meet the mission statement of;
'Saving neurons now!'
http://dev.biologists.org/content/early/2012/01/12/dev.072272.abstract

Summary

Rest (RE1-silencing transcription factor, also called Nrsf) is involved in the maintenance of the undifferentiated state of neuronal stem/progenitor cells in vitro by preventing precocious expression of neuronal genes. However, the function of Rest during neurogenesis in vivo remains to be elucidated because of the early embryonic lethal phenotype of conventional Rest knockout mice. In the present study, we have generated Rest conditional knockout mice, which allow the effect of genetic ablation of Rest during embryonic neurogenesis to be examined in vivo. We show that Rest plays a role in suppressing the expression of neuronal genes in cultured neuronal cells in vitro, as well as in non-neuronal cells outside of the central nervous system, but that it is dispensable for embryonic neurogenesis in vivo. Our findings highlight the significance of extrinsic signals for the proper intrinsic regulation of neuronal gene expression levels in the specification of cell fate during embryonic neurogenesis in vivo.