Reference 1

Selected sections from
Advances in Nutritional Medicine
June 1999, vol 10.
Food Biochemistry Reserach UK

A specially designed enriched environment for the induction of neuronal regeneration in MSA-P, Shy-Drager Syndrome and Parkinsonís disease.
John Grinstein
Biochemistry Research Institute
United Kingdom

Neurogenesis is a novel term used to indicate that new neurons can be generated in the central nervous system. This process has been demonstrated to actually occur in the hippocampus of mice, monkeys and humans. Experimental studies using bromodeoxyuridine as a marker have demonstrated its incorporation into newly generated DNA showing that DNA replication and neuronal division takes place in specific areas of the brain. These results have been thoroughly confirmed in a number of experimental studies that have eventually changed the neuroscientist dogma stating that neurones can not replicate.
These results have raised interest in trying to establish methods to modulate neuro-genesis because of its implications in developing improved treatments for neuro-degenerative disorders like Multiple System Atrophy (MSA) and Parkinsonís disease.
Utilizing BDUR as a DNA marker it has been possible to demonstrate in mice that neuro-genesis can be modulated through an enriched environment. Mice living in this type of environment for a period of 100 days were able to activate the process of neurogenesis in the hypothalamus. A 30% to 50% increase in the number of newly generated neurones was found in mice living in this type of environment compared to 10% to 15% of newly generated neurons in mice living in a standard environment.

The main symptoms of Shy-Drager Syndrome, Parkinsonís disease and MSA appear after the depletion of specific neurotransmitters that are necessary to send out signals for body movements or for the functionality of the autonomic nervous system. 
Medications that activate the biosynthesis of the neurotransmitter dopamine, will produce a temporary relief in Parkinsonís disease. However, its continuous use, will gradually inhibit the endogenous biosynthesis of this type of neurotransmitter. Increasing dosages of these types of drugs are required after each year and the disease progresses quickly at rates much higher than that of the natural progression of the disease. 

With the induction of neurogenesis, newly generated neurons will actively synthesize the missing neurotransmitters and the symptoms of the disease gradually disappear. Patients are able to function normally, without requiring any form of medication for many hours during the day, because a larger number of neuronal sites are now actively synthesizing all the necessary neurotransmitters.  
This normalization in biochemical brain activity can occur because of two main well established processes. A.- Neuronal restoration; that is when damaged neurons are able to repair themselves  or B.- Neurogenesis; that is when new neurons are generated in the damaged areas of the nervous system. 

Our studies have demonstrated that specific dietary interventions can enhance the secretion of brain neurotrophic factors. These factors are secreted by glial cells, that are adjacent to neurons and secrete factors that are necessary to maintain and provide nutrients and repair neurons.
Neurotrophic factors, secreted by brain astrocytes (glial cells), exert at least four types of action on the damaged or degenerating nigrostriatal dopaminergic system.
1. - Protection against dopaminergic neurotoxins.
2. - Stimulation of neuronal growth or axonal sprouting.
3. - Stimulatory effect on the metabolism and function of dopaminergic neurons.
4. - Increased Tyrosine Hydroxylase enzyme levels and dopamine synthesis and turnover.

A wide number of neurotrophic factors secreted by glial cells have been identified, characterized and shown to protect nigral dopamine neurons:
1. Glial cell Derived Neurotrophic Factor, (GDNF).
2. Neurturin.
3. Basic fibroblast growth factor (bFGF). 
4. Brain-derived neurotrophic factor (BDNF.
5. Neurotrophins 3 and 4/5. 
6. Ciliary neurotrophic factor.
7. Transforming growth factor-β (beta).

B.- Generation of new neurons or Neurogenesis
An enriched living environment has been shown to stimulate neurogenesis. Dietary interventions and exercise have also been shown to stimulate the process of neurogenesis. This process has been widely demonstrated to occur in experimental research with mice and monkeys.  Physical activity and exercising, practiced in conjunction with specific dietary interventions, can stimulate neurogenesis in humans. This can be easily observed in Parkinsonís disease and MSA patients, by measuring the gradual disappearance of disability. 
To establish if a specific enriched environment could induce the restoration of brain function and normalize neurotransmitter biosynthesis, we have designed MSA and Parkinsonís disease enriched environment protocols, involving:
1.- dietary interventions,
2.- the use of glial cells regenerative factors like GCRF,
3.- nutritional adjustments and
4.- analytical chemistry studies relating to external environmental factors to determine the etiology of the disease.

A definitive answer to demonstrate clinically that new neurons have been generated or damaged neurons have been repaired, can be provided with the use of Positron Emission Tomography, PET scan.
PET scan has proved to be the most important tool yet devised for experimental investigation of the living brain, whether healthy, traumatized, or diseased.
PET scans are tomographic images, formed by computer analysis of photons, detected from annihilation of positrons emitted by radionuclides incorporated into biochemical substances. The images often quantitfied with a colour scale, show the uptake and distribution of the substances in the tissue, permitting analysis and localization of metabolic and physiological function.