Chapter 14

Any person who studies human beings from a physical view point is likely to consider the living body, it's components, and the complexity of how the system brings itself forth and maintains itself.

As well we contemplate and value the domains of the living

The marvellous complexity of the body and the inter-relationships of its components require exquisite and amazing signalling and control systems.

Gregory Bateson among others drew our attention to the cybernetic nature of living systems, and Humberto Maturana and Francesco Varela added crucial descriptions about the autopoiesis and the necessary structure -function relationships of a system that runs itself in a "closed way".

The system evidently has a phenomenal potential to develop all of the functions that we call perception, cognition and recognition, memory and the phenomena that we call thinking and associated languaging.

The body is a biological system. The body, including the brain, is the physical dwelling place for the three other aspects of the self. Through the body we act out and manifest the feelings of the emotional self, the thoughts of the intellect, and the presence of the spiritual self.
The following are characteristics of the PHYSICAL SELF:

* Composed of the elements of the physical universe and subject to its physical laws and conditions

* Carrier of genetic information

* Interconnected with the mind through neurological and biochemical feedback
(Wilber would describe the mind as emergent) He would also describe the neural complexity as the "exterior of a system, and consciousness is what the system is from within (i.e. its interior)"
* Functions in the domains of sensing, action, and multi-level communication.

* Behaviourally expresses thoughts, language and feelings

* Repository for the memories of all experiences, including thoughts and feelings (that which is conserved in the living neural system)

* At times manifests physical symptoms of unresolved conflicts between intellect and emotions

I want to spend a little time considering the neural system, existing as it must in a body that supports it, and possessing connections beyond any dreamed of until fairly recently.

Ideas and constructs that arose in endocrinology, electrophysiology, neural transmission, molecular biology, the nature of transmitters and their specific receptors, nutrition, genetics (now covering gene function, regulation and gene product consequences as a dynamic changing system) growth and cell death, as well as neurology and wide-ranging neurosciences enter our conceptual fields.

We have some 100 billion nerve cells in our brains and perhaps almost all of them arose by the time we were born.

We now know that there are growth factors that influence the growth of these cells, and that some stem neural cells do exist in our brains.

For a longer time we have known that under situations of adequate nutritional factors, neural growth is protected, but stimuli in each type of neural circuitry increase dendritic proliferation, extending connections to more and more other neurones.

This is associated with enhanced and superior function in the cells and the human abilities seem to be extending, such that we can measure the area of the brain subserving the finger control of violinists as exhibiting increased size and function associated with this accomplishment.

Recently several psychologists have measured increased intelligence quotients in children of this generation when compared with their parents.

This is being picked up as children achieve milestones earlier than did their parents.

Another consideration is the discovery that there are some nine times as many glial cells in the brain as there are nerve cells.

These cells certainly possess crucial functions in terms of a two-way communication with nerve cells, as well as functions such as regulation of nutrient entry, immunological functions and even effects on synapse development.

Glial cells are of mesenchymal origin, but do exhibit voltage sensitive ion channels.

Much of their function however is using chemical type signalling.

Normally there is a concentration of calcium outside cells that is some 10,000 times greater than that inside the cells. Schwann cells do respond to synaptic firing and this involves some influx of calcium ions into the cells.

Calcium concentration in astrocytes rises when glutamate (an excitatory neuro-transmitter) is added to cell cultures.

The main storage form of cell energy is adenosine triphosphate (ATP), but this seems to be released at synaptic sites along with neurotransmitters.

 

 

When astrocytes are excited, they release ATP into their surroundings, and it binds to receptors on nearby astrocytes. This allows ion channels to open and sets of a chain reaction of responses across a population of astrocytes.

Fields and his colleagues at U of Maryland's Neurosciences group, show that this is associated with gene activation in glial cells and the functional consequences of this.

Field went on to show that when immature Schwann cells were cultured, they proliferated more slowly when axones were more active, and myelination of fibres was blocked.

Gallo and colleagues in an adjacent laboratory found that adenosine, (which is left when the phosphate of ATP is removed) does stimulate cells to mature and form myelin.

We then have the hope that stimulating neural circuits to fire and using adenosine or related compounds might help in healing after attacks of multiple sclerosis.

It should be noted that neurotransmitters do not drift out of their synaptic sites.

Glial cells such astrocytes may serve to amplify neural signals locally. This might well reinforce local memory circuits.

A protein called thrombospondin also spurs synapse formation.

Comparisons of brains reveals that the proportion of glial cells to neurons increases greatly as animals move up the evolutionary ladder.

I am strongly in favour of people providing optimum nutrition for their neural and glial cells, coupled with life interests and novel stimuli, which invite increased synaptic connections.

As well one is trying to counter free radical injury to cells such as has been demonstrated in many neuro-degenerative disorders.

Mitochondrial DNA is 10 times as susceptible to free radical injury as is nuclear DNA.

Coenzyme Q10
It is well known that coenzyme Q10 (ubiquinol-10) acts as an electron carrier of the mitochondrial respiratory chain. Moreover, the mitochondria-protecting action of ubiquinol-10 was confirmed by the finding that ubiquinone reduced to ubiquinol in the electron transport chain strongly inhibits lipid peroxidation in isolated organelles. As summarized by Frei et al., "The data of this study and all the evidence for antioxidant function of ubiquinol published over the last three decades strongly suggest that ubiquinol-10 contributes significantly to antioxidant defences in biology, complementing the antioxidant activities of -tocopherol by scavenging free lipid radicals and, possibly, by recycling -tocopherol."

More recently, Bliznakov comments that since the mitochondrial theory of aging has gained considerable acceptance, attention should be paid by gerontologists to the
importance of coenzyme Q10 in both its roles, that is, support of ATP biosynthesis in the mitochondrial inner membrane (thus preserving cellular integrity and function) and very effective scavenging of ROS.

Alpha-Lipoic Acid
This is a very interesting compound, because it is a normal component of mitochondria, where it forms the prosthetic group of coenzyme-A (CoA). Alpha-lipoic acid (ALA) is a relatively small molecule (MW 206), very hydrophobic, and with an -S-S- group, the antioxidant action of which was shown by the finding that ALA prevents the pathological results of vitamin C deficiency in guinea pigs and of
vitamin E in rats.

As recently reviewed by Packer et al., several studies in various model systems have shown that ALA is a powerful neutralizer of ROS such as the OHo free radical, hypochlorous acid, and singlet oxygen.

Moreover, ALA has preventive effects on diabetic microangiopathy and protects against skin senescence and age-related cognitive deficits. In view of the above, we feel that the probable protective effects of ALA on intramitochondrial thiol-redox homeostasis (and related mitochondrial biogenesis and bioenergetic function) deserve further in-depth investigation.

Alpha lipoic acid 200 mgm twice a day can be used to quench peroxynitrite anions (ONOO-) and gamma tocopherol 300 mgm a day does the same thing. Alpha lipoic acid (ALA) converts into dihydrolipoic acid (DHLA) but both are capable of quenching free radicals covering antioxidant effects in both water and fat-soluble domains.

Glutathione, Thiazolidine Carboxylic Acid, and N-Acetylcysteine
The use of these three antioxidants in aging research derives from the finding reviewed elsewhere and confirmed by recent studies that aging is accompanied by a progressive oxidation of glutathione and other thiolic compounds in the tissues of both vertebrates and invertebrates. This results in changes of the redox (GSSG/GSH) ratio that are much more striking in the mitochondria than in the extra mitochondrial compartment and lead to oxidative damage of the mtDNA.

In our opinion, the above justifies the attempts to modulate the mitochondrial rate of aging, thus increasing maximum life span, by dietary administration of glutathione and related thiol containing compounds syndromes.
TP is a cyclic sulphur amino acid similar in structure to proline that acts as an antioxidant and free radical scavenger and, according to our above-mentioned work, has favourable effects on both longevity and physiological functions in Drosophila and mice. This early thiol-antioxidant work has been expanded by the finding that dietary administration of sulphur-containing antioxidants, such as GSH or a TP derivative (ATCM) to mice prevents the age-related loss of performance in a tightrope test, as well as two effects of aging on brain mitochondria, that is, increase in the GSSG/GSH ratio and oxidative damage to mtDNA.

Another mitochondria protecting effect of the thiolic antioxidants is a significant preservation of the activity of the liver respiratory enzymes of aging mice fed a NAC-supplemented diet.

I return to a plan which is neuroprotective.

A possible plan
1. D alpha tocopherol succinate, 500IU orally daily (needs another substance to deal with the generated vitamin E free radicals. (E.g. mixed tocopherols, gamma tocopherol, tocotrienols, vitamin C, alpha lipoic acid, and co Q10 could each carry out this function.) (See below)
2. Co enzyme Q10 100-300 mgm daily (paper in coenzymeQ10 conference, Boston1998) (enhances mitochondrial energetics and mitochondrial DNA repair, and mops up oxidized vitamin E)
Best buy is now Pharmafoods CoE Q10 with 150mg/caps (also fish and flaxseed oil and Vitamin E are in this product)

3. Plant flavonoids from many coloured vegetables, salads and fruits (especially beneficial)
e.g. B carotenes (carrots),
lycopenes (tomatoes)
quercetin (onions, ginkgo biloba)
anthocyanosides (bilberry)
proanthocyanidins (grape seed and pine bark)
I pick out bilberry as more likely to protect the eye, and as the product Thiocondria from Eagle has bilberry and 200mg of alpha lipoic acid it is a good choice.
I always recommend Vitamin C to make up for what we destroy in cooking.

4. Magnesium supplements.
Any leaking of calcium from its extracellular location into cells could increase injury, and I use magnesium supplements to help protect this,

(I distinguish a protective function of magnesium from the above physiological actions of calcium influx in glial cells)

5. Glutathione,
The glutathione comes from whey protein. I use Pharmafoods Isowhey.

6.Adenosine.
There may be some diseases where adenosine supplements make sense.

7.Methyl donors are needed in MTHFR disorders where homocysteine is elevated.
These are folic or folinic acid, methyl cobalamin and trimethylglycine.

If the evidence supports exercise, listening to appropriate music such as Mozart's music, and taking up mind-body exercises, which we enjoy then why not, go for it?

A recent program on "happiness" showed that a scientist who moved to a Buddhist community and spent 6 hours per day meditating, was demonstrated by a MRI SPECT type study to show instant ability to turn on a so called happiness (bliss) area in his brain.

Maybe there really is a balance between spending time in learning and creating and other times of utter simplicity such as the "one taste' described by Ken Wilber.

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john.graham@flinders.edu.au

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