View Full Version : "In the period following birth, the human brain..."


mildadhd
05-23-13, 12:06 PM
In the period following birth,

the human brain,

unlike that of the chimpanzee,

continues to grow at the same rate as in the womb.

There are times in the first year of life when,

every second,

multiple millions of nerve connections,

or synapses,

are established.

Three-quarters of our brain growth takes place outside the womb,

most of it in the early years.

By three years of age,

the brain has reached 90 per cent of the adult size,

whereas the body is only 18 per cent of adult size. (See notes*)

This explosion in growth outside the womb gives us a far higher potential

for learning and adaptability than is granted to other mammals.


Notes: B. Perry and R. Pollard, "Homeostasis, Stress, Trauma and Adaptation: A Neurodevelopmental View of Childhood Trauma." Child and Adolescent Clinics of North America 7(1) (January 1998): 33-51. Citing data form R. Shore, Rethinking the Brain: New Insights into Early Development (New York: Families and Work Institute, 1997).



-Gabor Mate M.D., "In The Realm Of Hungry Ghosts", p 182


i!i

atSWIMtooboreds
05-23-13, 04:57 PM
...And?

I would get a lot more from your posts, I think, if you gave them some sort of context or wrote more of them yourselves rather than just quoting. I never know if there's some relationship you see between them and some discussion that's been going on, or whether they're just for everyone's enjoyment, or what.

SB_UK
05-24-13, 03:45 AM
Just thinking out loud.

Absolutely positive that ADHD represents an inappropriate stress response (squirming and zoning out - ADHD and ADD-I).

At this point we run into a very significant problem - is ADHD imprinted by environment (ie stressed out parent stresses child) from:

gestation (third trimester) [deranged maternal metabolism through stress resulting in wildly fluctuating blood glucose levels]
->- through ->-
the first three years of life [deranged parental-child interaction through parental stress resulting in sub-optimal oxytocin production/pair-bonding failure/feelings of security in child]
->- into ->-
education (4 yrs to 35 yrs) [you will study pointless facts which make no sense]
->- followed by ->-
money worries (30-65 yrs) [will you be able to pay the mortgage ? negative equity ? why has your pension provider gone bust ?]
->- at which point ->-
chronic disease (30 yrs to death) takes over [pain! pain! pain!]

So - persistent, chronic exposure to stress at each and every point in life - which'd lead to the body's ability to handle stress being undermined.

However - we can go back a stage beyond conception - into parental germ cell production - where it's been shown - that eg stress at certain points in life (see Marcus Pembrey) results in changes to the germ-line which are inherited.

We know that the genome of simple organisms responds to stressor by mutation (eg bacterial attempts to circumvent antibiotic or HIV to evade anti-viral drug) - and so it'd be crazy to suggest that there isn't some mechanism in the more evolved species (of man) to maximize survival prospects in the presence of stressor.

The only stressor to man (from an evolutionary point of view) should be lack of access to food.

The lowest tier of the Maslow pyramid represents food and shelter - and shelter's really not so big a problem given a tree and moving to someplace warm like the South of France :-).

So - food food food - availability is the only stressor which we need to consider.

Moreso - Pembrey has shown that food availability at a certain point (around puberty) encodes greater likelihood of grandchildren developing/not developing diabetes.
Exactly the same conclusion drawn in the Dutch Hunger study - but not at puberty in grandparent on diabetes risk in grandchild - but food scarcity in mother during gestation of child - results in elevated diabetes risk directly in child.

References
Pembrey and grandfather/grandmother (http://bioethicsbytes.wordpress.com/2008/06/30/epigenetics-the-ghost-in-your-genes/) - grandchild effect and increased diabetes risk
Dutch hunger Winter (http://en.wikipedia.org/wiki/Dutch_famine_of_1944) and increased diabetes risk.

At first they found that life expectancy of grandchildren was directly affected by the diet of the grandparents. Fatal childhood diabetes was often associated with their father’s father living during a period of reduced food supply. In a further development, the records revealed that triggering of a trans-generational effect was dependent upon the time in the grandparents’ lives when food had been in short supply. For the grandfather it was just before puberty and for the grandmother it was the moment of conception, crucial moments in the development of sperm and egg. These observations suggest that environmental information, in this case supply of food, was being imprinted on the DNA of the sperm and egg, providing strong evidence that epigenetic inheritance occurs in humans.
in Britain, found that the children of pregnant women exposed to famine were more susceptible to diabetes, obesity, cardiovascular disease, microalbuminuria and other health problems.

So - we've the entirely attractive idea that the genome encodes the capacity to (in response to stress which doesn't kill the organism off) - to maximize survival prospects (of the individual, next, next+1 generation) by reducing the food required (the traditional stressor) to survive - however that in the presence of food (that is where the mind/brain/body is taking the psych stressor (see list above) as physiological stressor) - diabetes results (pretty much as described in the 'thrifty gene hypothesis').

-*-

So - we can place the genetic/genomic/epigenomic argument as primary to the environmental argument - 'genetics' selects for more efficient metabolic system in the presence of stress (including psych. stress - the body can't differentiate from cortisol produced through psych/phys stress) - where 'environment' (abundance of food - turns a metabolic engine (in entirely the wrong way) which is geared towards survival in low food availability into diabetes).

So - the obvious question is - how ?? can 'stress' result in selection of an organism which requires less energy - that's a bit like suggesting that we can have 2 identical cars - one which does 50 mpg - the other 10 mpg - that's just not possible - unless we're looking at 2 identical cars (superficially) - running on different fuels. So - a petrol and an electric car can look identical - but there are significant differences under the hood - in their metabolic preference.

The fuel of starvation is the ketone - in starvation the ketone is elevated - and so it makes sense that with starvation - a biochemical system 'd be developed which operates over the ketone.

The Inuit and Mount Athos (2 very healthy populations) run on only ketones.
ref - Inuit/ketosis - all over internet.
ref - Mount Athos monks and ketosis - on pubmed

The ketone (or ketosis) as biochemical state (if vegan ketogenic) is considered healthy.
ref - Nutrition data website referenced study in video 'vegan Atkins (eco-Atkins) diet'

So - what if we're simply looking at the emergence (underlying all Western diseases including ADHD) of an organism which seeks to be in ketosis ?

Sounds good.

How ?
Through cortisol sensitivity.

But but but!
Psych. stress 'd have a terrible effect on a novel biochemistry which revolves around unswerving blood glucose levels (to maintain ketosis); it's well known that we're easily knocked out of ketosis by blood glucose fluctuation (eg eating hyperglycaemically).

So - all of the various stressors (money etc) listed above would certainly serve to make things worse for us - with the only solution open to us being - eating a vegan ketogenic diet, living a ketosis lifestyle (exercising,starvation) - living a life without unmanageable stress to allow us to maintain ketosis (it's well known that bad stress worsens a diabetic's capacity to control blood glucose levels).

-*-

So ... ... and once again - the idea permeates down - that a certain profile of food (ketogenic vegan), lifestyle (pro-ketogenic) and absence in unmanageable psych.stress (see the list above)
- is the route to solving not only ADHD but also the entire series of Western disorders.

-*-

Under the cover - the epigenomic change referenced by ADHD is an advantage - enhances survival fitness - but only in a world of moral austerity ... ... in a social environment of immoral (only money) excesses (meat and potato alcohol laced sugared pastries) ... ... we die horrible deaths.

-*-

How hard is it to maintain ketosis in an immoral/psych. stressful world ?
Really hard.

(Psych.) stress triggers food intake, triggers stress-relief (the meat and potato pie) ... ... prevents the mind from allowing the body to settle into its required metabolic state.

-*-
Re: "In the period following birth, the human brain..."

So - certainly - this is a problem - but a downstream problem which occurs as a consequence of a competitive psych. stressful societal infrastructure.

SB_UK
05-24-13, 05:08 AM
Things're getting a little bit more complicated again ... ...

http://www.sciencemag.org/content/339/6116/211.abstract
Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitorhttp://en.wikipedia.org/wiki/Histone_deacetylase_inhibitor
HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics. More recently they are being investigated as possible treatments for cancers and inflammatory diseases.So - screaming out is the transition of man from growth to maintenance - revolving around Insulin/IGF-1 (the insulin paradigm) to ketosis (driving b-hydroxybutyrate into our system).
http://www.ncbi.nlm.nih.gov/books/NBK3869/
Oxidative Stress and Aging



What's the problem with ketosis ?
People want to eat.

Why ?
Reward system - blood glucose elevation.

But don't we trasncend the blood glucose elevation (primitive) reward system upon enlightenment/pair-bonding ?
Yes.

So - you're suggesting that we're freed from primitive reward system to eat to ketosis (as long as we're not psych. stressed - requiring change in societal infrastructure).
OK

- but there's something (still) that doesn't feel right about this idea.

SB_UK
05-24-13, 06:20 AM
Administration of exogenous βOHB, or [eating to a ketogenic profile], fasting or calorie restriction, two conditions associated with increased βOHB abundance ...
... ... treatment of mice with βOHB conferred substantial protection against oxidative stress. Oxidative stress can only really mean 'chilled out' mitochondria.

Why are mitochondria chilled out in a ketogenic environment ?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867088/
The Ketogenic Diet: Stoking the [mitochondrial] Powerhouse of the CellEliminating fluctuations in cortisol 'd mean eliminating fluctuations in blood glucose and plasma ionic concentrations (including proton) (the two things which cortisol as glucocorticoid and mineralocorticoid do) - the mitochondria wants a stable intracellular ionic environment and isn't really interested in glycolysis running alone without feeding it (oxidative phosphorylation) - because eg lactic acid production (local acid production) from anaerobic glycolysis - sets up an acidic environment - which stresses the mitochondria (makes them work ever faster) out.
http://www.biology.arizona.edu/biochemistry/problem_sets/metabolism/05t.html
If you isolate mitochondria and place them in buffer with a low pH they begin to manufacture ATP. Why?
Permeability of outer membrane
Mitochondrial production of ATP requires a concentration gradient of H+, with a high concentration at the inter membrane space and a low concentration in the matrix. The inner membrane is is impermeable to H+, but the outer membrane of the mitochondria will allow H+ to pass through.
Thus, placing mitochondria in a low pH buffer produces a H+ gradient that can generate ATP through ATP synthetase.
So high intracellular pH stresses out mitochondria.
And low intracellular pH (ie lowered protomotive force) 'd reduce the protomotive force - reducing level of oxidative phosphorylation ?

And ... ...
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1179957/
The relationship between pHi and pHo under these conditions was linear, steep (0.63 pHi/pHo) and remarkably similar to the response predicted from a passive cell model (i.e. a cell lacking pHi regulation). and so as extracellular pH drops - so does intracellular pH - meaning that an extracellular acidic environment will lead to mitochondrial oxidative stress - through the intracellular environment tracking extracellular environment ('remarkably similar to the response predicted from a passive cell model') and becoming more acidic.

-*-

http://mjiri.tums.ac.ir/browse.php?a_id=932&slc_lang=en&sid=1&ftxt=1
Keeping a constant intracellular [H+]/[OH-] at 37 degrees C requires buffering systems that sustain intracellular pH around 6.8-6.9; this is facilitated by keeping arerial blood pH at about 7.4.-*-

So - we've an ideal pH of 6.8 (neutrality at 37 degress C) for mitochondria being chilled out - with decreasing pH - the mitochondria work faster ... ... and there's plenty of information (https://www.google.com/search?q=alkaline+intracellular&ie=utf-8&oe=utf-8&aq=t&rls=org.mozilla:en-GB:official&client=firefox-a) around the internet which suggests that alkaline pH (>7) intracellularly results in a switch between mitochondrial electron transport chain and aerobic glycolysis (associated with cancer).

Why ? Mitochondria can't cut it when alkaline pH raises - ie reduced protomotive force - results in insufficient oomph to power the mitochondria into ATP generation.

Another of those balance is key problems ... ... what'd cause alkaline intracellular ph ?
Metabolic alkalois occurs with increased cortisol production.
pH(intracellular) tracks pH(extracellular) - so cortisol is responsible for elevated intracellular pH ?

From ... ...
http://hyper.ahajournals.org/content/35/5/1099.full

http://hyper.ahajournals.org/content/35/5/1099/F2.medium.gif

"Recordings of intracellular pH (pHi) were made by video fluorescence microscopy. Aldosterone (0.5 nmol/L) rapidly increased pHi
The increments on pHi for each cortisol concentration were similar to those observed for aldosterone."

-*-

Aaarghhh!!!

So - bringing it all together -- what's going on ??

We need a constant intracellular pH of 6.8 (neutrality at 37 degrees C) for the mitochondria to operate. Chronic stress hormone production implies changes to the extracellular pH which will have effects either way (reduced or increased intracellular pH). Switching into ketosis is pro-mitochondrial - but cannot be maintained in either chronic physical or psychological stress - alleviating chronic (unmanageable) stresses 'd result in human metabolism settling upon a metabolic state - ketogenic (beta-hydroxybutyrate is a mood stabilizer (ah! so this'd be the mechanism of valproic acid in epilepsy/bipolar disorder and also explain why so many anti-epileptics eg lamictal make it over into treamtment of bipolar disorder)) - which we're best suited to.

Now - correct issues like mood - and the parent is freed to do what the parent 'd do in the absence of stress - and that is to behave like a parent and not a stress-crazed money-crazed fool.

Valproic Acid is also a histone deacetylase inhibitor and is under investigation for treatment of HIV and various cancers.

-*-

A life without societal hierarchy through eliminating money/law.
And a life of eating not particularly much - with vegan ketogenic screaming out as the optimal choice.

SB_UK
05-24-13, 07:46 AM
http://high-fat-nutrition.blogspot.co.uk/search/label/Cholesterol%20fed%20rabbit
[The rabbit] is a fibre-vore which runs its metabolism on free fatty acids derived from cellulose fermentation in its hind gut, usually eating Timothy Grass as its sole food.

Maybe - given the right gut bacteria - we're just the same as them.

Human colonic bacteria ferment RS and nonstarch polysaccharides (NSP; major components of dietary fiber) to short-chain fatty acids (SCFA), mainly acetate, propionate, and butyrate.

It'd make a lot of sense !

SB_UK
05-24-13, 08:26 AM
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145060/
contribution of scfa directly to energy metabolism

It has been estimated that scfa produced in the colon principally upon fermentation of non-digestible carbohydrates by the resident microbiota contributes about 10% of daily energy requirements in man.

The main scfa are acetate, propionate, and butyrate, in that order.

Butyrate is an important energy source for the colonic mucosa and plays a role in epigenetic control of gene expression through the inhibition of histone deacetylase... ...Just 10% :(
Connection between beta-hydroxybutyrate and butyrate is begging to be made -<- mood stabilizing

Vegan ketogenic could tick all the boxes 'cept for the meat and potato pastry addicts ... ...

It really does feel as though there's a fight between lil' carbs and lil' fats for our metabolic needs - where lil' fats are the good guys.