Infection as PD cause/Lipopolysaccharide
The hypothesis proposed here suggests that Parkinson's Disease may be acquired in the womb as the result of fetal exposure to maternal stress-related hormones and maternal immune-related cytokines. This "multi-hit" origin combined with the necessity of proper timing in relation to the "opening" of specific developmental "windows" accounts for the often baffling patterns observed in the distribution of Parkinson's Disease. Reverett123 (talk) 01:17, 13 October 2012 (UTC)
Niehaus  reported a case of PD in a human (herself) induced by LPS contamination.
In March 1995 a 22 year old biological laboratory assistant named Ines Niehaus was accidentally infected with LPS, which spilled out of a test tube and entered her through an open cut in her thumb. One hour later she showed the first signs of illness, which developed into neurological symptoms. Six weeks after the accident she was diagnosed with Parkinson’s Disease. As a trained scientist she was able to keep an accurate record of the progress of her illness and the effects of the treatments she tried.
Carvey et al  have suggested that exposure to neurotoxins while still in utero may represent a risk factor for PD.
They noted that, exposure to the bacteriotoxin, lipopolysaccharide(LPS) during a critical developmental window in rats, leads to the birth of animals with fewer than normal dopamine (DA) neurons.
This DA neuron loss is apparently permanent as it is still present in 16 months old animals (the longest period studied to date). Moreover, the loss of DA neurons seen in these animals increases with age thereby mimicking the progressive pattern of cell loss seen in human PD. The DA neuron loss is accompanied by reductions in striatal DA, increases in DA activity, and increased production of the pro-inflammatory cytokine Tumor Necrosis Factor alpha (TNF-alpha). These are also characteristics of the PD brain.
They go on to observe:-
A common complication of pregnancy is a condition known as bacterial vaginosis (BV), which is known to produce increased levels of LPS and pro-inflammatory cytokines in the chorioamniotic environment of the fetus. This raises the interesting possibility that BV may be a risk factor for PD. The possibility that prenatal toxin exposure may contribute to the development of a neurodegenerative disease of the aged raises interesting new pathogenic questions and draws attention to the possibility that in utero exposure to neurotoxins may represent a heretofore unrecognized cause of PD.
Ling et al  observed that the pro-inflammatory cytokine tumour necrosis factor alpha (TNFalpha) was elevated in the striatum of rats previously infected pre-natally with bacterial vaginosis. They went on to establish that these animals were more susceptible to subsequent DA neurotoxin exposure.
We conclude that prenatal exposure to LPS produces a long-lived THir cell loss that is accompanied by an inflammatory state that leads to further DA neuron loss following subsequent neurotoxin exposure. The results suggest that individuals exposed to LPS prenatally, as might occur had their mother had bacterial vaginosis, would be at increased risk for Parkinson's disease.
Qin et al  set out to investigate the effects of LPS.
A single systemic lipopolysaccharide (LPS, 5 mg/kg, i.p.) or tumor necrosis factor alpha (TNFalpha, 0.25 mg/kg, i.p.) injection was administered in adult wild-type mice and in mice lacking TNFalpha receptors (TNF R1/R2(-/-)).....Systemic TNFalpha and LPS administration activated microglia and LPS reduced the number of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra (SN) by 23% at 7-months post-treatment, which progressed to 47% at 10 months. increased expression of brain pro-inflammatory factors..... Together, these data demonstrate that through TNFalpha, peripheral inflammation in adult animals can: (1) activate brain microglia to produce chronically elevated pro-inflammatory factors; (2) induce delayed and progressive loss of DA neurons in the SN. These findings provide valuable insight into the potential pathogenesis and self-propelling nature of Parkinson's disease.
An anonymous paper on a Wordpress site ,  quotes Freidenberg 1993:-
Sensitivity to LPS is genetically determined, varying considerably among different species. The sensitivity of normal animals (mice) to endotoxin may be enhanced considerably under different experimental conditions that include treatment with live (infection) or killed Gram-negative and -positive bacteria.
And Carvey 2004
We conclude that prenatal exposure to LPS produces a long-lived THir cell loss that is accompanied by an inflammatory state that leads to further DA neuron loss following subsequent neurotoxin exposure. The results suggest that individuals exposed to LPS prenatally, as might occur had their mother had bacterial vaginosis, would be at increased risk for Parkinson’s disease.
Thus, this disrupted immune system can lead to chronic inflammation and microglial activation with elevated levels of cytokines and related pro-inflammatory chemicals leading to “cell death. The twin roots (immune and endocrine) of Parkinson’s Disease reaching back to the earliest moments of existence represent the extreme of a spectrum of causal scenarios and produce the earliest onset of symptoms. The two arise together and interact to produce the disorder by means of a self-perpetuating immune-endocrine reaction.
• Liu and Bing  carried out a comprehensive (70 item bibliography) review of the evidence connecting LPS and PD, albeit based on animal models, and enumerate the pathological sequences. Their conclusions state:-
Mechanisms underlying the LPS PD models are investigated and indicated that LPS induces microglial activation, activated microglia release proinflammatory and neurotoxic factors such as IL-1, TNF-α, IL-6, and NO to cause neuronal damage, and damaged neuron may emit injury signals such as neuromelanin and abnormal α-synuclein to trigger reactive microgliosis. This neuronal-microglial interaction may be reinforced and become a self-amplifying cycle to result in progressive dopaminergic neurodegeneration.
Cai et al  induced PD symptoms in laboratory rats by neo-natal injections of LPS.
Use this table to search for other relevant data which can be added to this page
|SEARCH WORDS||PUBMED||PUBMED CENTRAL||GOOGLE SCHOLAR|
|Parkinson's bacterial vaginosis||Yes||Yes||Yes|
- Niehaus, Ines (2001) Full TextPoster presentation at the XIV International Congress on Parkinson's Disease in Helsinki, Finland, 2001 Parkinsonism caused by Lipopolysaccharides of Salmonella Minnesota (a Case Report) http://www.endotoxin.gmxhome.de/artikel3.htm
- Carvey, P. M.; Chang, Q.; Lipton, J. W. amd Ling. Z. (2003) Abstract Front. Biosci. 1; 8: s826-37. Prenatal exposure to the bacteriotoxin lipopolysaccharide leads to long-term losses of dopamine neurons in offspring: a potential, new model of Parkinson's disease. http://www.ncbi.nlm.nih.gov/pubmed?term=12957870
- Ling, Z. D.; Chang, Q.; Lipton, J. W.; Tong, C. W.; Landers, T. M. and Carvey, P.M. (2004) Abstract Neuroscience. 124 (3) 619 - 628. Combined toxicity of prenatal bacterial endotoxin exposure and postnatal 6-hydroxydopamine in the adult rat midbrain. http://www.ncbi.nlm.nih.gov/pubmed/14980732
- Qin, L.; Wu, X.; Block, M. L.; Liu, Y.; Breese, G. R.; Hong, J.; Knapp, D. J. and Crews, F. T. (2007) Abstract Glia. 55 (5) 453 - 462. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. http://www.ncbi.nlm.nih.gov/pubmed/17203472
- (2011) Full Text Prenatal Beginnings of Parkinson’s Disease http://amatterofbalance.wordpress.com/2011/03/23/prenatal-beginnings-of-parkinsons-disease/
- Liu, Mei and Bing, Guoying (2011) Full Text Parkinsons Dis. 2011; 2011: 327089. Published online 2011 April 27. doi: 10.4061/2011/327089 Lipopolysaccharide Animal Models for Parkinson's Disease http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096023/
- Cai, Zhengwei; Fan, Lir-Wan; Kaizaki, Asuka; Tien, Lu-Tai; Ma, Tangeng, Pang, Yi Lin, Shuying; Lin,Rick. C.S. and Simpson, Kimberley S. (2013) Full Text Dev. Neurosc. 35 (0) 155 – 171 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777222/