[Conductor71]

I can't for the life of me recall how I stumbled upon pregnenolone, but stumble I did, and after researching it for a good hour, it has me wondering if we might not benefit from it as a supplement.

Pregnenolone is described on the Net as "the mother of all hormones". Indeed it is a precursor in the development of many of our hormones but is a steroid. What caught my attention is that it:

- is produced by cholesterol in our cellular mitochondria
- is both neuroprotective and neurotrophic
- acts as a natural GABA antagonist (several drugs acting as GABA antagonists are in clinical trials right now)- why important? this treats some of the most disabling symptoms like akinesia/freezing and gait problems
- modulates all of our neurotransmitters
- regulates synaptic transmissions

Further, it is hypothesized that as we age, our adrenals and central nervous system produce less of this neurosteroid leaving us vulnerable to neurodegenerative disease.

We in essence, are getting hit twice, our brain cells have missing or malfunctioning mitochondria, so in addition to normal attrition due to aging, our brain cells are most likely not even producing much pregnenolone due to disease. AD patients have low levels of both pregnenolone and DHEA but little if nothing has been researched in the PD patient. It is also interesting to note that it takes cholesterol or lipids to produce this neurosteroid, and people with low cholesterol LDL are more likely to develop PD.

See this article for the emerging role of neurosteroids (scroll down to Illuminating the role...)

Two very recent abstracts highlight how neurosteroids may play a role in treatment of PD.

Neuroactive steroid regulation of neurotransmitter release in the CNS: action, mechanism and possible significance.

Neurosteroid biosynthetic pathway changes in substantia nigra and caudate nucleus in Parkinson's disease.

What do y'all think? Should we be supplementing with Pregnenolone? I have read of DHEA protecting against neuronal loss in animal models, but we have nothhing else to go on...yet.

Laura

[paula_w]

Thanks for these laura. I've told my story many times - hormone shutdown [early menopause and hypothyroid] came before motor symptoms of PD. Very interesting.
I think it's ok to reprint pub med:


Prog Neurobiol. 2009 Oct;89(2):134-52. Epub 2009 Jul 10.
Neuroactive steroid regulation of neurotransmitter release in the CNS: action, mechanism and possible significance.

Zheng P.
State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China. pzheng@shmu.edu.cn
Abstract

Neuroactive steroids refer to steroids that are capable of regulating neuronal activities. Neuroactive steroids, synthesized either de novo in the nervous tissue or in the peripheral endocrine glands or as synthetic steroids, have exhibited numerous important modulatory effects on brain functions and brain diseases. At the cellular level, in addition to the effect on postsynaptic receptors, most neuroactive steroids, including pregnenolone, pregnenolone sulfate, progesterone, allopregnanolone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, testosterone and estradiol, have modulatory effects on the release of multiple neurotransmitters like glutamate, GABA, acetylcholine, norepinephrine, dopamine and 5-HT. Many of these effects occur in the brain regions involved in learning and memory, emotion, motivation, motor and cognition. Moreover, the effects are rather complicated, maybe depending on many factors such as types of neuroactive steroids, brain regions and presynaptic functional states. The mechanisms are also complicated. Many of them involve rapid non-genomic effects on presynaptic receptors and ion channels like sigma-1 receptor, alpha(1) receptor, nicotine receptor, D1 receptor, NMDA receptor, GABA(A) receptor and L-type Ca(2+) channels. These effects have made neuroactive steroids important regulators of synaptic transmission in the central nervous system and constitute the major basis for many important actions of neuroactive steroids on brain functions and brain diseases.

Brain Pathol. 2010 Sep;20(5):945-51. Epub 2010 Mar 19.
Neurosteroid biosynthetic pathway changes in substantia nigra and caudate nucleus in Parkinson's disease.

Luchetti S, Bossers K, Frajese GV, Swaab DF.
Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands. s.luchetti@nin.knaw.nl
Abstract

There is emerging evidence from animal studies for a neuroprotective role of sex steroids in neurodegenerative diseases, but studies in human brain are lacking. We have carried out an extensive study of the neurosteroid biosynthetic pathways in substantia nigra (SN), caudate nucleus (CN) and putamen (PU) of 7 Parkinson's disease (PD) patients and 7 matched controls. The mRNA levels of 37 genes including neurosteroid biosynthetic enzymes, hormone receptors and the neurosteroid-modulated gamma-amino-butyric acid -A (GABA-A) receptor subunits were analyzed by quantitative PCR (qPCR). In the SN, we found downregulation of 5alpha-reductase type 1 (5alpha-R1), sulfotransferase 2B1 (SULT2B1) and some GABA-A receptor subunits (alpha4, beta1) while in the CN, upregulation of 3alpha-hydroxysteroid dehydrogenase type 3 (3alpha-HSD3) and alpha4 GABA-A receptor subunit (22-fold) was observed. No significant differences were found in the PU. These data imply an involvement of pregnane steroids and changes in GABAergic neurotransmission in the neurodegenerative process and suggest that neurosteroids may deserve further investigation as potential therapeutic agents in PD.

PMID: 20406233 [PubMed - in process]

[Conductor71]

Originally Posted by paula_w

Thanks for these laura. I've told my story many times - hormone shutdown [early menopause and hypothyroid] came before motor symptoms of PD. Very interesting.
I think it's ok to reprint pub med:

Yes, the more I think about it; you are on the mark. This is why estrogen is touted as being so neuroprotective. These steroids also prove again how we should not think of neurology and endocrinology as two distinct fields any more; it should be studied as one discipline in medicine.

My story is that my PD worsened with pregnancy. It was odd because my motor symptoms did not change (until recently); my tremor worsened, but mainly it was that my metabolism changed with the meds. I had my son and whoa all of a sudden I am eating Sinemet like M & M's.

Pregnenolone is available as a supplement, but I am a little wary of experimentation when something is known as the progenitor of all hormones. It is marketed and sold in Europe though as a cognitive enhancement. It is also in clinical trials for the treatment of schizophrenia which we know may have a dopamine dysregulation connection, so I guess it is safe to try.

I'd like to think that we'll read more about how these neurosteroids may help us in the future, but the skeptic in me says that there's no moolah in it, so it will languish along with all the other things found freely in nature that may benefit us. At the very least it establishes how important our hormones are and how essential lipids are to a healthy brain.

Laura

[paula_w]

How do we go about getting something researched without being wealthy?

Silly question and yet that's where we live.

[reverett123]

Originally Posted by paula_w

How do we go about getting something researched without being wealthy?

Silly question and yet that's where we live.

The hard part is getting any one to listen.
About "neurosteroids"- or neuroactive steroids, as I have called them, are a subset of neuroactive hormones. They are "hormones" because they are produced by the endocrine glands and they are "neuroactive" because they affect the behavior of the nervous system.

But it is bigger than that because the immune system is in the dance as well via the production of neuroactive cytokines. So these three systems are constantly influencing one another and each time they do it feeds back into the dance.

There is one other dancer at the PD Ball - the GI system and the factors such as the fatty acids and a hundred other nutrients that originate there.

But the lines blur. Eat some coconut oil (GI) and the pancreas turns out some insulin (endocrine). Get a bug (immune) and the stress response (endocrine) is affected. And it all whirls around the nervous system.