Mr Duck:

Everett makes a point here although I am inclined to agree with you on most points. Would you mind posting your CV so that we might evaluate your background?

All the best

Lloyd

Mr Duck
I am curious to know how you managed to do these experiments to get such definitive answers. Did you publish your data and if not, could you give more info> I am a biochemist and a PWP and interested in neurogenesis; Also I would love to know how you did this work without any funding.

girija


When I studied every cell type, I purposefully checked to see whether mitosis ("neurogenesis" in neurons) occurred in each type, and at what ages it occurred and ceased. All cell types reproduce in humans. However, four of them do not reproduce in adults. The well known one is teeth, which cease reproducing in adults and younger. The cells involved in Parkinson's Disease (the dopaminergic neurons) are another of those four cell types well known not to reproduce. This fact is the basis for the stem cell theorists.

Yes sure, as long as everyone else here does the same.

Girija, the answer to your first question is that I did not carry out the experiments that established that dopaminergic neurons do not reproduce in adults. It was already in the scientific literature.

In order to write a complete human biochemistry it would have been physically impossible to complete it by doing all practical work. Therefore, I did not need any of the costly equipment and physical resources that you would normally need. I compiled it by systematically going through all types of biochemical structure (vitamins, fatty acids, amino acids, etc) and then each system in the body (nervous, cardiovascular, endocrine, etc), cell by cell, using all existing research - this involved the analysis and piecing together of hundreds of thousands of books and research papers over more than ten years. I spent a further three years, virtually seven days a week, morning to night, on writing a complete biochemistry of Parkinson's Disease. I did this using the same methods. I initially used major London University libraries. Much of the time I was not actually allowed to, but managed to repeatedly trick my way in to the library Universities to do the work. When they finally caught on, and I was prevented from using all the London University libararies, I ended up solely in the British Library, which allows anyone to use their resources - even me - free of charge. The British Library staff got to know me well, and went out of their way to help me find the hundreds of thousands of books and research papers I used, despite my never telling them what I was doing. In the final months I had to ration my visits to the British Library because I could not even afford the bus fare. I had to walk much of the way to save money. When I completed the work on Parkinson's Disease I was penniless.

It is great to read all of you participating to this debate and giving your own conceptions even when with huge passion.
It changes from other subjects no one seems to understand the interest of, and it demonstrates how difficult it is for all of us to make choices when learning and avoid t get involved in new beliefs as well as to get rid of old credos.

The only goal here is to keep all the time properly informed.

Here are three articles about neurogenesis in the adult mammalian substantia nigra, all of them with full text links given.
Questions and remarks to come after.

Shan X, Chi L, Bishop M, Luo C, Lien L, Zhang Z, Liu R.
Enhanced de novo neurogenesis and dopaminergic neurogenesis in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease-like mice.
Stem Cells. 2006 May;24(5):1280-7.

Research reports on de novo neurogenesis, particularly dopaminergic (DA) neurogenesis in the adult mammalian substantia nigra (SN), remain very controversial. For this reason, we used the nestin second intron enhancer-controlled LacZ reporter transgenic mouse model coupled with the 1-methyl-4-phyenyl-1,2,3,6-tetrahydropyridine (MPTP) lesion system to investigate whether there are neurogenesis and DA neurogenesis in the SN of the adult normal and Parkinson’s disease (PD)-like mice. First, we demonstrated the presence of neural progenitor cells (NPCs), basal levels of neurogenesis, and DA neurogenesis in the normal adult mouse SN. Second, we showed that there is not only a significant increase in the number of NPCs but also a dramatic increase of neurogenesis from the NPCs in the SN and the midline region adjacent to the SN of the PD-like mice compared with that of normal controls. More importantly, we also demonstrated that there is an increase of DA neurogenesis in the SN of the MPTP-lesioned mice. Third, we showed that the increased DA neurogenesis in the MPTP-lesioned mice was derived from the NPCs and 5-bromodeoxyuridine-positive cells, suggesting that multiple stem cell lineages may contribute to the enhanced neurogenesis in the adult SN. Taken together, these results establish that there are basal levels, albeit low, and increased levels of de novo neurogenesis and DA neurogenesis in the SN of the adult normal and PD-like mice, respectively. The increased NPCs in the MPTP-lesioned mice further suggest that experimental approaches to promote de novo neurogenesis may provide an effective therapy for PD by functional replacement of degenerated DA neurons.

full text = http://stemcells.alphamedpress.org/c...full/24/5/1280


Zhao M, Momma S, Delfani K, Carlen M, Cassidy RM, Johansson CB, Brismar H, Shupliakov O, Frisen J, Janson AM.
Evidence for neurogenesis in the adult mammalian substantia nigra.
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7925-30.


New neurons are generated from stem cells in a few regions of the adult mammalian brain. Here we provide evidence for the generation of dopaminergic projection neurons of the type that are lost in Parkinson's disease from stem cells in the adult rodent brain and show that the rate of neurogenesis is increased after a lesion. The number of new neurons generated under physiological conditions in substantia nigra pars compacta was found to be several orders of magnitude smaller than in the granular cell layer of the dentate gyrus of the hippocampus. However, if the rate of neuronal turnover is constant, the entire population of dopaminergic neurons in substantia nigra could be replaced during the lifespan of a mouse. These data indicate that neurogenesis in the adult brain is more widespread than previously thought and may have implications for our understanding of the pathogenesis and treatment of neurodegenerative disorders such as Parkinson's disease.

Full text = http://www.pnas.org/cgi/content/full/100/13/7925



Borta A, Hoglinger GU.
Dopamine and adult neurogenesis.
J Neurochem. 2007 Feb;100(3):587-95.

Dopamine is an important neurotransmitter implicated in the regulation of mood, motivation and movement. We have reviewed here recent data suggesting that dopamine, in addition to being a neurotransmitter, also plays a role in the regulation of endogenous neurogenesis in the adult mammalian brain. In addition, we approach a highly controversial question: can the adult human brain use neurogenesis to replace the dopaminergic neurones in the substantia nigra that are lost in Parkinson's disease?

Full text = http://www.blackwell-synergy.com/act....x&cookieSet=1

Neurogenesis - Changing your mind:

During most of the 20th century,

leading scientists theorized that brain cells didn’t divide like other cells in the body. It was generally understood that neurons could not be added to the brain after earliest childhood. A respected proponent of this theory was Pasko Rakic, chairman of the Neurobiology Department at Yale University, whose research in the early 1980s concluded that no new neurons were being formed in the brains of adult primates.

However, in light of recent research, many neuroscientists (including Rakic) have had, shall we say, a change of mind.

“I think the fact that there are so many neurons that are produced . . . suggests that they must play some important function, because it wouldn’t make sense for the brain to expend so much energy to make these new cells if they’re not going to be used.”

—Elizabeth Gould at the 2002 Annual Convention of the American Psychological Association, quoted in APA's Monitor on Psychology, November 2002




By studying the detrimental effects of chronic stress on the brains of rats and primates, Princeton University psychology professor Elizabeth Gould has observed inexplicable evidence of the brain’s capacity to heal itself by the creation of new neurons—a process called neurogenesis.

Gould has demonstrated that the brain’s mechanisms are affected by its surroundings. Jonah Lehrer, highlighting Gould’s work in an article for the February-March 2006 issue of Seed magazine titled “The Reinvention of the Self,” uses the term “environ-mental conditions.” He describes Gould’s discoveries: “The structure of our brain, from the details of our dendrites to the density of our hippocampus, is incredibly influenced by our surroundings. Put a primate under stressful conditions, and its brain begins to starve. It stops creating new cells. The cells it already has retreat inwards. The mind is disfigured.”

If the brain structure is hurt by stressful or negative “environ-mental” conditions, can its functions be helped, even healed, by positive “environ-mental” forces? As Lehrer points out, the social implications of this cutting-edge study of neurogenesis are enormous.

THE SCIENCE OF DEPRESSION

Ronald Duman, professor of psychiatry and pharmacology at Yale University and an expert on depression, studies the molecular and cellular changes caused by stress as well as by the use of antidepressants. In a 2001 report published in the Journal of Pharmacology and Experimental Therapeutics, he, too, concluded that “decreased rates of cell proliferation are seen in response to stress.” He also noted that “drugs, as well as hormones and growth factors, can regulate the rate of cell proliferation.”

But he questioned whether a shortage of serotonin is the root cause of depression—an assumption that underlies the science behind antidepressant drugs. In an article titled “Antidepressants and Neuroplasticity” in the June 2002 issue of the journal Bipolar Disorders, Duman and colleague Carrol D’Sa proposed that, based on their studies, the reason antidepressants work is not because they cause a surge in serotonin (which should, but doesn’t, result in an immediate lessening of the symptoms of depression) but because they promote the production of trophic factors, proteins that lead to neurogenesis. In other words, by encouraging new cell growth, the drugs enhance the brain’s plasticity, or ability to adapt and thus cope.

Duman’s research is causing a change in the way neuroscience views depression. It has also led to further studies linking neurogenesis, depression and stress. In one study, Gould and her team deprived newborn rats of their mothers for either 15 minutes or three hours a day, placing a high level of stress on the infant rodents. Of those who were separated for the longer period, they reported: “Our results suggest that early adverse experience inhibits structural plasticity . . . and diminishes the ability of the hippocampus to respond to stress in adulthood” (Nature Neuroscience, August 2004). In other words, the rats never recovered their ability to deal with high levels of stress—in this case the early absence of their mother. Chronic stress debilitates dendrites, inhibits cell production and causes atrophy of the hippocampus, a part of the brain essential for learning and memory and also implicated in mood disorders, whereas access to a nurturing adult contributed directly to the development of healthy brain structure and function.

Lehrer remarks that “neurogenesis is an optimistic idea.” But Gould’s team, having demonstrated that deprivation and stress have negative and long-lasting consequences, is now showing that “the brain, like skin, can heal itself.” Lehrer goes on to note that Gould is “finding hopeful antidotes to neurogenesis-inhibiting injuries. ‘My hunch is that a lot of these abnormalities [caused by stress] can be fixed in adulthood,’ she says. ‘I think that there’s a lot of evidence for the resiliency of the brain.’”

MAKING THE CONNECTION

In another study, Gould and her coworkers studied the brains of adult marmosets. Some of the animals were housed in large enclosures that featured natural vegetation and encouraged foraging. Others were kept in standard laboratory cages. When the team compared the brains of animals from each group, they reported finding “dramatic differences in structural plasticity.” The marmosets that were used to the more complex environments were found not only to have more connections between neurons but also to experience a higher rate of neurogenesis than the ones that were kept in stark lab cages. When the caged animals were transferred from their bleak environment to the more natural, enriched setting, they responded with changes in their brain chemistry: the rate of new cell growth in their brains increased.

Much remains to be discovered as researchers continue their studies in this fascinating field. But if various kinds of deprivation can be shown to cause deterioration in the dendrites of the brain, wouldn’t an environment that is enriched by kindness, caring and love also contribute to the construction or regeneration of a healthy brain?

Are we not discovering that we can literally change our minds? Neuroscience may be stumbling across some spiritual truths; the positive power of love and concern that the Creator God intended us to experience and exemplify could actually regenerate the human brain.

Consider in addition that the Hebrew Scriptures and Apostolic Writings are replete with calls for individuals to repent of their harmful attitudes and actions. Do repentant people experience both physical and spiritual benefits from changing their ways?

That certainly appears to be Paul’s message when he writes in Romans 12:2
that we should “be transformed by the renewing of [our] mind”!

THOMAS E. FITZPATRICK
thomas.fitzpatrick@visionjournal.org

http://www.nature.com/nrn/journal/v8...F4E139DE7FDA43

Nature Reviews Neuroscience 8, 221-232 (March 2007) | doi:10.1038/nrn2054

The neuropoietic cytokine family in development, plasticity, disease and injury
Sylvian Bauer1,2, Bradley J. Kerr2,3 and Paul H. Patterson4 About the authors

Top of page
Abstract

Neuropoietic cytokines are well known for their role in the control of neuronal, glial and immune responses to injury or disease. Since this discovery, it has emerged that several of these proteins are also involved in nervous system development, in particular in the regulation of neurogenesis and stem cell fate. Recent data indicate that these proteins have yet more functions, as key modulators of synaptic plasticity and of various behaviours. In addition, neuropoietic cytokines might be a factor in the aetiology of psychiatric disorders.

Mr Daffy Duck,

I have many questions to ask you, and not to loose anyone's time, here is my very first one
" Who are you really as a person, most probably totally different from Duffy Duck , this poor little black duck you are hiding behind, described by the Warner Bros as a "maniac, explosive, and unpredictable self-analytical, competitive, peevish, paranoid, and neurotic personality?"
I do not believe one second you may be like him, in no way.
http://looneytunes.warnerbros.com/we...tars_daffy.jsp
(Please excuse my poor english, not my maternal tongue, I am trying to say things the better, and the way I feel them so I do hope you will be indulgent to me).

Your demonstration of how rough and tough scientists may be toward anyone who dares to have any idea or use other words and manners than the traditional ones to present them is fantastic one, a lesson to youngers. I wonder if you have not suffered of any exclusion because of your own ideas in other places at other times....
Anyhow, you have totally convinced me that you are far the best here to judge amateur works like ours .........so the best one too to be able to make them climb steps to be professional-like and so valuable enough to be then discussed in any very strict-minded assembly.

Even when the first impression you have reported did not look like an encouraging one, ("When a medical theory does not have a sound scientific basis, has no evidence in support of it, and is inconsistent with all known facts, there is nothing to choose from".), I am sure you are not on Neurotalks for any other reason than to serve and to give your help somewhere, at least enough to ask you now my second request,
"Would you agree for exchanging points of view on personal e-mails? I would be honoured and pleased if you accept to share few hours "pour la bonne cause"."

Day has come yet and sun is raising.
It is so late for me , here in Lyon, to go on writing; I need to rest at leasr for a while, (btw, are you a PwP's yourself, Mr DD?) but will come tomorrow afternoon to argue and give complete references about the neuropathological works of Braak, Jellinger, Wakabayashi, Takahashi and many others (see below) as well as about a very recent publication of A.E Lang, the first one to integrate these data in etiopathogenic works.

A.E.LANG
The progression of Parkinson disease: a hypothesis.
Neurology. 2007 Mar 20;68(12):948-52.


" Here are some lines about Braak's neuropathological classification has clarified the true extent of illness in brain, characterized by a uniform propagation in six different stages pattern for IPD process spreading.through body and brain following a specific route.

Though neuropathology studies have described the whole course of the spreading process more than a decade ago and despite it has been settled that “there are no cases of PD in which neurodegeneration occurs only in the substantia nigra and in which there are no Lewy Bodies*” [* = Wakabayashi & Takahashi -Parkinsonism Relat Disord. 2005 Jun;11 Suppl 1:S31-7) ], most scientific works and related publications are and remain ignorant of these data, still focuse upon SNpc involvement and keep asserting the common though appearingly erroneous belief that the PD underlying process starts in SNpc, that SNpc is the initial area to be damaged in PD .


Such a focus upon dopaminergic neurons and related motor impairments has been the rule since almost the beginning of PD history and remains, in most works, the strongest consideration.
However, as far as thirty years ago, in 1976, Ohama has demonstrated with the histochemical fluorescence method upon rats brain, that the distribution of Lewy bodies in Parkinson's disease correspond, surprisingly well, to the one of monoamine cell bodies (dopamine, noradrenaline and serotonin) .

Since then, it has been wiedly proven that Lewy bodies are to be found elsewhere in brain than in SNpc and out of brain too.
- In ganglion cells of the colonic myenteric plexus, Kupsky W.J, 1987
- Widely in the Auerbach's and Meissner's plexuses (stomach) , Wakabayashi, 1989
- Degeneration of the preganglionic parasympathetic neurons innervating the internal **** sphincter , Oyanagi K., 1990
- Dorsal vagal nucleus and sympathetic ganglia , Gibbs W.R, 1991
- Sympathetic ganglia, enteric nervous system of the alimentary tract and the submandibular ganglion, Takeda S., 1993
- Widely distributed in the hypothalamus, sympathetic system (intermediolateral nucleus of the thoracic cord and sympathetic ganglia) and parasympathetic system (dorsal vagal and sacral parasympathetic nuclei) and in the enteric nervous system of the alimentary tract, cardiac plexus, pelvic plexus and adrenal medulla. Wakabayashi, 1997

Giving a major contribution to knowledge and understandings about PD, the neuropathology works of H. Braak & E. Braak have clearly described since 1996 the pattern of brain destruction to be a systematically hierarchised spreading one as first starting in stomach wall, DMNX (dorsal motor nucleus nervus vagus) and OB (olfactory bulb)……

(Pattern of brain destruction in Parkinson's and Alzheimer's diseases, Braak & Braak, 1996;
Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson's disease : preclinical and clinical stages,Braak, 2002
Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology, Braak, 2006.)

At last, other works have largely confirm Braak's staging of LB-pathology in PD and added other considerations to the initial pattern with different morphological lesion patterns for the clinical subtypes of PD (Jellinger K.A).

a) The akinetic-rigid type shows more severe cell loss in the ventrolateral part of substantia nigra zona compacta (SNZC) that projects to the dorsal putamen than the medial part projecting to caudate nucleus and anterior putamen, with negative correlation between SNZC cell counts, severity of akinesia-rigidity, and dopamine loss in the posterior putamen. Reduced dopaminergic input causes overactivity of the GABA ergic inhibitory striatal neurons projecting via the "indirect loop" to SN zona reticulata (SNZR) and medial pallidum (GPI) leading to inhibition of the glutamatergic thalamo-cortical motor loop and reduced cortical activation.

b) The tremor-dominant type shows more severe neuron loss in medial than in lateral SNZC and damage to the retrorubral field A8 containing only few tyrosine hydroxylase and dopamine transporter immunoreactive (IR) neurons but mainly calretinin-IR cells. A8 that is rather preserved in rigid-akinetic PD (protective role of calcium-binding protein?) projects to the matrix of dorsolateral striatum and ventromedial thalamus. Together with area A10 it influences the strial efflux via SNZR to thalamus and from there to prefrontal cortex ".


Last words and I'll fall asleep on my keyboard :
We are fighting neither for THE TRUTH nor for the GLORY of Science but for OUR TRUTH that is to ameliorate our quality of life.
Please, give everything to have hearts as rigourous as minds, and Never forget that " On ne voit bien qu'avec le coeur; l'essentiel est invisible aux yeux." Antoine de Saint-Exupéry

(It is only with the heart that one can see rightly; what is essential is invisible to the eye)
Anne.

Dear Ann,
I have two mutations of my Parkin2 gene, deletion of exxons 3, and 5.
Can you explain how this plays into the currect studies?

Sincerely,
Vicky

Thanks Anne, that was excellent!