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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diverse and independently-varying signs of Parkinson's disease (PD) are often attributed to one simple mechanism: degeneration of the dopaminergic innervation of the posterolateral striatum. However, growing recognition of the dopamine (DA) loss and other pathology in extra-striatal brain regions has led to uncertainty whether loss of DA in the striatum is sufficient to cause parkinsonian signs. We tested this hypothesis by infusing cis-flupenthixol (cis-flu; a broad-spectrum D1/D2 receptor antagonist) into different regions of the macaque putamen (3 hemispheres of 2 monkeys) while the animal performed a visually-cued choice reaction time task in which visual cues indicated the arm to reach with and the peripheral target to contact to obtain food reward. Following reward delivery, the animal was required to self-initiate release of the peripheral target and return of the chosen hand to its home position (i.e., without the benefit of external sensory cues or immediate rewards). Infusions of cis-flu at 15 of 26 sites induced prolongations of reaction time (9 of 15 cases), movement duration (6 cases), and/or dwell time of the hand at the peripheral target (8 cases). Dwell times were affected more severely (+95%) than visually-triggered reaction times or movement durations (+25% and +15%, respectively). Specifically, the animal's hand often 'froze' at the peripheral target for up to 25-s, similar to the akinetic freezing episodes observed in PD patients. Across injections, slowing of self-initiation did not correlate in severity with prolongations of visually-triggered reaction time or movement duration, although the latter two were correlated with each other. Episodes of slowed self-initiation appeared primarily in the arm contralateral to the injected hemisphere and were not associated with increased muscle co-contraction or global alterations in behavioral state (i.e., inattention or reduced motivation), consistent with the idea that these episodes reflected a fundamental impairment of movement initiation. We found no evidence for an anatomic topography within the putamen for the effects elicited. We conclude that acute focal blockade of DA transmission in the putamen is sufficient to induce marked akinesia-like impairments. Furthermore, different classes of impairments can be induced independently, suggesting that specific parkinsonian signs have unique pathophysiologic substrates.
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PMID:Testing the contributions of striatal dopamine loss to the genesis of parkinsonian signs. 2249 34

The ultimate causes of idiopathic Parkinson's disease (PD) are not fully known, but environmental and occupational causes are suspected. Postencephalitic parkinsonism has been linked to influenza, and other viral infections have also been suspected to relate to PD. We estimated the relationship between PD and both infections and possible vectors of infection (i.e., animal and human) in a population-based, case-control study in British Columbia, Canada. We recruited 403 cases detected by their use of antiparkinsonian medications and 405 controls from the registrants of the provincial universal health insurance plan. Severe influenza was associated with PD (odds ratio [OR]: 2.01; 95% confidence interval [CI]: 1.16-3.48), although this effect was attenuated when reports were restricted to those occurring 10 or more years before diagnosis. Childhood illnesses were inversely associated with PD, particularly red measles (OR: 0.65; 95% CI: 0.48-0.90). Several animal exposures were associated with PD, with statistically significant effects for cats (OR: 2.06; 95% CI: 1.09-3.92) and cattle (OR: 2.23; 95% CI: 1.22-4.09). Influenza infection may be associated with PD. The inverse relationships with childhood infections may suggest an increased risk with subclinical or asymptomatic childhood infections. Occupational exposure to animals may increase risk through transmission of infections or may indicate exposure to another agent of interest (e.g., bacterial endotoxin).
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PMID:Association of Parkinson's disease with infections and occupational exposure to possible vectors. 2275 66

A growing body of epidemiologic and experimental data point to chronic bacterial and viral infections as possible risk factors for neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Infections of the central nervous system, especially those characterized by a chronic progressive course, may produce multiple damage in infected and neighbouring cells. The activation of inflammatory processes and host immune responses cause chronic damage resulting in alterations of neuronal function and viability, but different pathogens can also directly trigger neurotoxic pathways. Indeed, viral and microbial agents have been reported to produce molecular hallmarks of neurodegeneration, such as the production and deposit of misfolded protein aggregates, oxidative stress, deficient autophagic processes, synaptopathies and neuronal death. These effects may act in synergy with other recognized risk factors, such as aging, concomitant metabolic diseases and the host's specific genetic signature. This review will focus on the contribution given to neurodegeneration by herpes simplex type-1, human immunodeficiency and influenza viruses, and by Chlamydia pneumoniae.
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PMID:Infectious agents and neurodegeneration. 2289 88

The world witnessed the influenza virus during the seasonal epidemics and pandemics. The current strain of H1N1 (swine flu) pandemic is believed to be the legacy of the influenza pandemic (1918-19). The influenza virus has been implicated in many neuropsychiatric disorders. In view of the recent pandemic, it would be interesting to review the neuropsychiatric aspects of influenza, specifically swine flu. Author used popular search engine 'PUBMED' to search for published articles with different MeSH terms using Boolean operator (AND). Among these, a selective review of the published literature was done. Acute manifestations of swine flu varied from behavioral changes, fear of misdiagnosis during outbreak, neurological features like seizures, encephalopathy, encephalitis, transverse myelitis, aseptic meningitis, multiple sclerosis, and Guillian-Barre Syndrome. Among the chronic manifestations, schizophrenia, Parkinson's disease, mood disorder, dementia, and mental retardation have been hypothesized. Further research is required to understand the etiological hypothesis of the chronic manifestations of influenza. The author urges neuroscientists around the world to make use of the current swine flu pandemic as an opportunity for further research.
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PMID:The neuropsychiatric aspects of influenza/swine flu: A selective review. 2327 61

Genetic evidence links mutations in the LRRK2 gene with an increased risk of Parkinson's disease, for which no neuroprotective or neurorestorative therapies currently exist. While the role of LRRK2 in normal cellular function has yet to be fully described, evidence suggests involvement with immune and kidney functions. A comparative study of LRRK2-deficient and wild type rats investigated the influence that this gene has on the phenotype of these rats. Significant weight gain in the LRRK2 null rats was observed and was accompanied by significant increases in insulin and insulin-like growth factors. Additionally, LRRK2-deficient rats displayed kidney morphological and histopathological alterations in the renal tubule epithelial cells of all animals assessed. These perturbations in renal morphology were accompanied by significant decreases of lipocalin-2, in both the urine and plasma of knockout animals. Significant alterations in the cellular composition of the spleen between LRRK2 knockout and wild type animals were identified by immunophenotyping and were associated with subtle differences in response to dual infection with rat-adapted influenza virus (RAIV) and Streptococcus pneumoniae. Ontological pathway analysis of LRRK2 across metabolic and kidney processes and pathological categories suggested that the thioredoxin network may play a role in perturbing these organ systems. The phenotype of the LRRK2 null rat is suggestive of a complex biology influencing metabolism, immune function and kidney homeostasis. These data need to be extended to better understand the role of the kinase domain or other biological functions of the gene to better inform the development of pharmacological inhibitors.
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PMID:Leucine-rich repeat kinase 2 (LRRK2)-deficient rats exhibit renal tubule injury and perturbations in metabolic and immunological homeostasis. 2379 78

In 1961, David C. Poskanzer and Robert S. Schwab presented a paper, "Studies in the epidemiology of Parkinson's disease predicting its disappearance as a major clinical entity by 1980." This paper introduced the hypothesis that Parkinson's disease was derived from a single aetiology, the influenza virus. We review the original Poskanzer and Schwab hypothesis that Parkinson's disease was based on the association between the 1918-19 influenza epidemic and the later observation of Parkinsonism in some influenza sufferers. We also further explore the prediction that Parkinson's disease would totally disappear as an entity once original influenza victims were all deceased. Current research has revealed that there are many potential causes and factors important in the occurrence of Parkinson's disease, postencephalitic Parkinsonism, and encephalitis lethargica. Poskanzer and Schwab presented a novel hypothesis; however, it was proven false by a combination of research and time.
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PMID:The Demise of Poskanzer and Schwab's Influenza Theory on the Pathogenesis of Parkinson's Disease. 2385 34

The depth, pattern, timing and duration of unconsciousness, including sleep, vary greatly in inflammatory disease, and are regarded as reliable indicators of disease severity. Similarly, these indicators are applicable to the encephalopathies of sepsis, malaria, and trypanosomiasis, and to viral diseases such as influenza and AIDS. They are also applicable to sterile neuroinflammatory states, including Alzheimer's disease, Parkinson's disease, traumatic brain injury, stroke and type-2 diabetes, as well as in iatrogenic brain states following brain irradiation and chemotherapy. Here we make the case that the cycles of unconsciousness that constitute normal sleep, as well as its aberrations, which range from sickness behavior through daytime sleepiness to the coma of inflammatory disease states, have common origins that involve increased inflammatory cytokines and consequent insulin resistance and loss of appetite due to reduction in orexigenic activity. Orexin reduction has broad implications, which are as yet little appreciated in the chronic inflammatory conditions listed, whether they be infectious or sterile in origin. Not only is reduction in orexin levels characterized by loss of appetite, it is associated with inappropriate and excessive sleep and, when dramatic and chronic, leads to coma. Moreover, such reduction is associated with impaired cognition and a reduction in motor control. We propose that advanced understanding and appreciation of the importance of orexin as a key regulator of pathways involved in the maintenance of normal appetite, sleep patterns, cognition, and motor control may afford novel treatment opportunities.
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PMID:Inflammation-sleep interface in brain disease: TNF, insulin, orexin. 2465 19

Disruption of neuronal iron homeostasis and oxidative stress are closely related to the pathogenesis of Parkinson's disease (PD). Ginkgetin, a natural biflavonoid isolated from leaves of Ginkgo biloba L, has many known effects, including anti-inflammatory, anti-influenza virus, and anti-fungal activities, but its underlying mechanism of the neuroprotective effects in PD remains unclear. The present study utilized PD models induced by 1-methyl-4-phenylpyridinium (MPP(+)) and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to explore the neuroprotective ability of ginkgetin in vivo and in vitro. Our results showed that ginkgetin could provide significant protection from MPP(+)-induced cell damage in vitro by decreasing the levels of intracellular reactive oxygen species and maintaining mitochondrial membrane potential. Meanwhile, ginkgetin dramatically inhibited cell apoptosis induced by MPP+ through the caspase-3 and Bcl2/Bax pathway. Moreover, ginkgetin significantly improved sensorimotor coordination in a mouse PD model induced by MPTP by dramatically inhibiting the decrease of tyrosine hydroxylase expression in the substantia nigra and superoxide dismutase activity in the striatum. Interestingly, ginkgetin could strongly chelate ferrous ion and thereby inhibit the increase of the intracellular labile iron pool through downregulating L-ferritin and upregulating transferrin receptor 1. These results indicate that the neuroprotective mechanism of ginkgetin against neurological injury induced by MPTP occurs via regulating iron homeostasis. Therefore, ginkgetin may provide neuroprotective therapy for PD and iron metabolism disorder related diseases.
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PMID:Neuroprotective effects of ginkgetin against neuroinjury in Parkinson's disease model induced by MPTP via chelating iron. 2596 39

Parkinson's disease (PD) may take decades to develop and early life exposures such as infection may be important. However, few epidemiological studies have evaluated early life risk factors in relation to PD risk. We therefore examined such associations in a prospective analysis of 3 545 612 individuals born in Sweden between 1932 and 1970 without PD on January 1, 2002. Incident PD cases were identified using the Swedish Patient Register during 2002-2010. Information on sibship size, number of older and younger siblings, multiple births, parental age, birth month and season was obtained from the Swedish Multi-Generation Register. Monthly data on national burden of influenza-like illness during 1932-1970 were obtained from the Swedish Public Health Agency. Hazard ratios with 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. During the follow-up, 8779 incident PD cases were identified. As expected, older age, male sex, parental occupation as farmers, and family history of PD were associated with higher PD risk. Overall, early life factors, including flu burden in the year of birth, were not associated with PD risk, although we did find a lower PD risk among participants with older siblings than those without (HR = 0.93, 95%CI: 0.89, 0.98). Our study therefore provided little support for important etiological contributions of early life factors to the PD risk late in life. The finding of a lower PD risk among individuals with older siblings will need confirmation and further investigation.
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PMID:Early-Life Factors and Risk of Parkinson's Disease: A Register-Based Cohort Study. 2708 11

Reactive oxygen species (ROS) are essential molecules for many physiological functions and act as second messengers in a large variety of tissues. An imbalance in the production and elimination of ROS is associated with human diseases including neurodegenerative disorders. In the last years the notion that neurodegenerative diseases are accompanied by chronic viral infections, which may result in an increase of neurodegenerative diseases progression, emerged. It is known in literature that enhanced viral infection risk, observed during neurodegeneration, is partly due to the increase of ROS accumulation in brain cells. However, the molecular mechanisms of viral infection, occurring during the progression of neurodegeneration, remain unclear. In this review, we discuss the recent knowledge regarding the role of influenza, herpes simplex virus type-1, and retroviruses infection in ROS/RNS-mediated Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS).
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PMID:Redox Imbalance and Viral Infections in Neurodegenerative Diseases. 2711 Mar 25


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