Aces NR3C1methylation.

[sarahb12]

A while back, maybe on the 23 discussion group, many were worried about their ACES (# traumatic events in life) I think this may explain why.

http://m.nautil.us/issue/47/consciousne ... -a-disease

The NR3C1 gets methylated either during fetal development or childhood events before or during adolescence. It seems the answer is what many of us thought (BDNF -excercise and other ways ) for brain issues - it increases hippocampus and grows neurons.

I wonder if there is a way to un-methylate this?

Sarah

[sarahb12]

It looks like exercise does increase expression of NR3C1. At least in stressed mice. Increased expression makes me think me it's no longer turned off, and hopefully somewhat permanent.

https://molecularbrain.biomedcentral.co ... 015-0128-8

[Julie G]

Powerful article, Sarah. As someone with a less than optimal ACES score, it resonates strongly with me. It also reminded me of the Neural Retraining work being done by Annie Hopper. I've never formally used her approach, but found simply processing her 12 steps to be liberating. That said, my guess is that mindful repetition would be key. (See my notes from the Dynamic Bain Coference below.)

I was fascinated by Annie Hopper's work. She's recovered from CIRS via a moldy building and a toxin exposure and now works on healing others by re-training the limbic system of the brain. Her claim is that when the brain is assaulted by "whatever" (a physical injury, biotoxin, other toxin, virus, etc.) the brain can automatically go into a fight (fight vs. flight) response and get stuck there even when the initial injury has been healed. She even has some data that "unsticking" the limbic system can h-e-a-l the brain without other traditional therapies.

It occurred to me that this may be very relevant for our shared gene, other assaults withstanding. Dr. Bredesen's lab has done lots of work on ApoE4 as a transcription factor. He uses some cool graphics in his talks and reveals that ApoE4 is RelA dominant. Immunologically, our RelA is always upregulated. He describes RelA as being North Korea ready to bomb and attack anything, even a sweet little kitty cat crossing their boundary. That's ApoE4. Our gene is pro-inflammatory, ready to attack. As we evolved from primates to hominids, that probably gave us an advantage. We came down from the trees onto the savannah and stepped onto dung and other nasties and our pro-inflammatory allele protected us. That advantage has likely become a disadvantage in our uber-hygenic world. We no longer have as many "real" threats so our body perceives benign influences as being threatening or over-responds to real threats. We become highly and chronically inflamed. Other APOE genotypes are SIRT1 dominant. He describes SIRT1 as being a hippy commune (remember Berkley? ) where everyone works together cooperatively for the greater good in peace and harmony. Very anything goes, very nurturing. Our goal, as ApoE4 carriers, is to downregulate RelA and uprelgulate SIRT1. That's why we take certain supplements like resveratrol and NAD. (Side note: Dr. Tanzi recommended NAD, nicotinamide riboside, to prevent AD.) Given our gene's physiological tendencies, it made me wonder if this limbic system "stuckness" could apply to us even more strongly than other APOE genotypes. Also, we know this chronic hyper-vigilance can lead to adrenal fatigue and mitochondrial downregulation; all an intrinsic part of ApoE4. Hopper is claiming to heal folks from chronic fatigue, orthostatic intolerance, fibromyalgia, and chemical sensitivities, among many other maladies.

You can learn more at her website, Dynamic Neural Retaining System. She also has a book called Wired for Healing - Remapping the Brain to Recover from Chronic and Mysterious Illnesses. I'm a big proponent of spending as little money as possible on these strategies so I took a photo of her bottom line recommendations for you all, shared below. Interesting stuff. I've already begun applying it in small ways with my self-chatter. She had some decent hard evidence (studies from Canada) and her patient recovery stories were impressive. I'll look for the studies and post as I find them. Did anybody else catch this lecture? I'm eager to hear your thoughts.

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[SusanJ]

Good find (I think ). It does reinforce the ACEs findings, that there is a real reason for lifelong, and generational impacts of chronic stressors. And in the book, Childhood Disrupted, Nakazawa points out that women are more prone to the effects because women's bodies, with higher estrogen and baseline levels of glucocorticoids (which help protect pregnancies), become less able to regulate inflammation when faced with chronic stress. Over time, this can also lead to higher autoantibodies and autoimmune disease, which is much higher in women than men.

Julie, I just checked and if one has Kindle Unlimited, the Hopper book is available free. Going to take a look, since we are having a snowy day and reading sounds like a good activity.

[sarahb12]

Here's a good article on ketamine.

https://blogs.scientificamerican.com/sc ... special-k/

[MarcR]

The relationship described in the article among ketamine, BDNF, and hippocampal neuroplasticity causes me to wonder if ketamine could help people suffering from hippocampal atrophy and associated difficulty forming new memories.

[sarahb12]

BDNF is supposed to increase hippocampus size (which decreases with AD).