The coincidence of schizophrenia and Parkinsonism: some neurochemical implications

1976 ◽  
Vol 6 (2) ◽  
pp. 227-233 ◽  
Author(s):  
T. J. Crow ◽  
Eve C. Johnstone ◽  
H. A. McClelland
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Corpus Striatum ◽  
Therapeutic Effects ◽  
Dopaminergic Transmission ◽  
Tuberculum Olfactorium ◽  
Dopaminergic Mechanisms ◽  
The Relationship ◽  
Increased Activity ◽  
The Brain

SynopsisThe hypothesis has recently been advanced that increased activity of central dopaminergic mechanisms underlies the symptomatology of the schizophrenias. The evidence that dopaminergic transmission in the corpus striatum is impaired in Parkinson's disease suggests that observations on the relationship between Parkinson's disease and schizophrenia may illuminate the pathophysiology of the latter disease. Four cases are reported in which an illness with schizophrenic features developed in the setting of longstanding Parkinson's disease; attention is drawn to earlier reports of schizophrenic illnesses occurring as.postencephalitic sequelae in the presence of a parkinsonian syndrome. These observations appear to conflict with the view that increased dopamine release in the striatum is necessary for the expression of schizophrenic psychopathology, but do not exclude the possibility that increased transmission may occur at other dopaminergic sites in the brain, for example the nucleus accumbens, tuberculum olfactorium or cerebral cortex. Similarly the dopamine receptor blockade hypothesis of the therapeutic effects of neuroleptic drugs cannot be maintained with respect to an action in the striatum in view of the differences between the actions of thioridazine and chlorpromazine in this structure, but may be tenable for actions at extra-striatal sites.

Lack of Association of Locus Coeruleus Pathology with Orthostatic Hypotension in Parkinson’s Disease

2020 ◽  
pp. 1-5
Author(s):  
Qiang Tong ◽  
Liam Chen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Orthostatic Hypotension ◽  
Locus Coeruleus ◽  
The Elderly ◽  
Motor Symptom ◽  
Postmortem Brains ◽  
The Relationship ◽  
The Brain

Orthostatic hypotension (OH) is a common non-motor symptom in Parkinson’s disease (PD) and is linked with increased mortality risk among the elderly. Although the locus coeruleus (LC) is the major source of noradrenaline (NA) modulation in the brain, its role in the pathogenesis of OH in PD remains largely elusive. Here we examined 44 well characterized postmortem brains of PD patients and available clinical data to explore the relationship between OH and LC pathology in PD. Our results failed to indicate that the LC pathology as well as the substantia nigra pathology were robustly associated with the presence of OH in PD patients, suggesting targeting LC norepinephrinergic system alone may not be sufficient to treat OH in PD.

scholarly journals Cellular and Molecular Mediators of Neuroinflammation in the Pathogenesis of Parkinson’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Sandeep Vasant More ◽  
Hemant Kumar ◽  
In Su Kim ◽  
Soo-Yeol Song ◽  
Dong-Kug Choi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Defense Mechanism ◽  
Neuronal Degeneration ◽  
Neuronal Damage ◽  
Normal Structure ◽  
Host Defense Mechanism ◽  
And Function ◽  
The Relationship ◽  
The Brain

Neuroinflammation is a host-defense mechanism associated with restoration of normal structure and function of the brain and neutralization of an insult. Increasing neuropathological and biochemical evidence from the brains of individuals with Parkinson’s disease (PD) provides strong evidence for activation of neuroinflammatory pathways. Microglia, the resident innate immune cells, may play a major role in the inflammatory process of the diseased brain of patients with PD. Although microglia forms the first line of defense for the neural parenchyma, uncontrolled activation of microglia may directly affect neurons by releasing various molecular mediators such as inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β), nitric oxide, prostaglandin E2, and reactive oxygen and nitrogen species. Moreover, recent studies have reported that activated microglia phagocytose not only damaged cell debris but also intact neighboring cells. This phenomenon further supports their active participation in self-enduring neuronal damage cycles. As the relationship between PD and neuroinflammation is being studied, there is a realization that both cellular and molecular mediators are most likely assisting pathological processes leading to disease progression. Here, we discuss mediators of neuroinflammation, which are known activators released from damaged parenchyma of the brain and result in neuronal degeneration in patients with PD.

scholarly journals Decrease in ITGA7 Levels Is Associated with an Increase in α-Synuclein Levels in an MPTP-Induced Parkinson’s Disease Mouse Model and SH-SY5Y Cells

2021 ◽  
Vol 22 (23) ◽  
pp. 12616
Author(s):  
Sangeun Han ◽  
Min Hyung Seo ◽  
Sabina Lim ◽  
Sujung Yeo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Expression Patterns ◽  
Alpha Synuclein ◽  
Control Group ◽  
Potential Association ◽  
Sirna Knockdown ◽  
The Relationship ◽  
The Brain

We investigated the potential association between integrin α7 (ITGA7) and alpha-synuclein (α-syn) in a methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) mouse model. Tyrosine hydroxylase (TH), ITGA7, and α-syn expression in the substantia nigra (SN) of the brain were observed to examine the pathological characteristics of PD. To determine the relationship between ITGA7 and PD, the expression of TH and α-syn was investigated after ITGA7 siRNA knockdown in SH-SY5Y cells. The ITGA7 microarray signal was decreased in the SN of the MPTP group, indicating reduced ITGA7 expression compared to that in the control. The expression patterns of ITGA7 in the control group and those of α-syn in the MPTP group were similar on immunohistochemical staining. Reduction in ITGA7 expression by ITGA7 siRNA administration induced a decrease in TH expression and an increase in α-syn expression in SH-SY5Y cells. The decreased expression of ITGA7 significantly decreased the expression of bcl2 and increased the bax/bcl2 ratio in SH-SY5Y cells. These results suggest that reduced ITGA7 expression may be related to increased α-syn expression and apoptosis of dopaminergic cells in an MPTP-induced PD mouse model. To the best of our knowledge, this is the first study to show an association between ITGA7 and PD.

scholarly journals Parkinson’s Disease and the Gut: Symptoms, Nutrition, and Microbiota

2021 ◽  
pp. 1-15
Author(s):  
Nehal Yemula ◽  
Celina Dietrich ◽  
Vaclav Dostal ◽  
Michael Hornberger
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gastrointestinal Tract ◽  
Supporting Evidence ◽  
Gastrointestinal Conditions ◽  
Nutrition And Diet ◽  
The Impact ◽  
The Relationship ◽  
The Brain ◽  
Symptoms And Signs

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, characterized by symptoms of bradykinesia, rigidity, postural instability, and tremor. Recently, there has been a growing focus on the relationship between the gut and the development of PD. Emerging to the forefront, an interesting concept has developed suggesting that the initial pathophysiological changes occur in the gastrointestinal tract before changes are seen within the brain. This review is aimed at highlighting the relationship between PD and the gastrointestinal tract, along with the supporting evidence for this. Firstly, we will focus on the gastrointestinal conditions and symptoms which commonly affects patients, including both upper and lower gastrointestinal issues. Secondly, the impact of nutrition and diet on neurological health and PD physiology, with particular emphasis on commonly consumed items including macronutrients and micronutrients. Finally, variability of the gut microbiome will also be discussed and its link with both the symptoms and signs of PD. The evidence presented in this review highly suggests that the initial pathogenesis in the gut may proceed the development of prodromal PD subtypes, and therefore building on this further could be imperative and lead to earlier diagnosis with new and improved therapeutics.

scholarly journals Current Approaches and Tools Used in Drug Development against Parkinson’s Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 897
Author(s):  
Oliwia Koszła ◽  
Piotr Stępnicki ◽  
Agata Zięba ◽  
Angelika Grudzińska ◽  
Dariusz Matosiuk ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Treatment Options ◽  
New Drugs ◽  
Computer Assisted ◽  
Therapeutic Effects ◽  
New Compounds ◽  
The Brain ◽  
Selection Of

Parkinson’s disease is a progressive neurodegenerative disorder characterized by the death of nerve cells in the substantia nigra of the brain. The treatment options for this disease are very limited as currently the treatment is mainly symptomatic, and the available drugs are not able to completely stop the progression of the disease but only to slow it down. There is still a need to search for new compounds with the most optimal pharmacological profile that would stop the rapidly progressing disease. An increasing understanding of Parkinson’s pathogenesis and the discovery of new molecular targets pave the way to develop new therapeutic agents. The use and selection of appropriate cell and animal models that better reflect pathogenic changes in the brain is a key aspect of the research. In addition, computer-assisted drug design methods are a promising approach to developing effective compounds with potential therapeutic effects. In light of the above, in this review, we present current approaches for developing new drugs for Parkinson’s disease.

Gene expression analysis in modeling Parkinson’s disease

2020 ◽  
pp. 103-104
Author(s):  
М.М. Руденок ◽  
А.Х. Алиева ◽  
А.А. Колачева ◽  
М.В. Угрюмов ◽  
П.А. Сломинский ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Systemic Disease ◽  
Molecular Genetic ◽  
Presymptomatic Stage ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome ◽  
The Brain ◽  
Transcriptome Level

Несмотря на очевидный прогресс, достигнутый в изучении молекулярно-генетических факторов и механизмов патогенеза болезни Паркинсона (БП), в настоящее время стало ясно, что нарушения в структуре ДНК не описывают весь спектр патологических изменений, наблюдаемых при развитии заболевания. В настоящее время показано, что существенное влияние на патогенез БП могут оказывать изменения на уровне транскриптома. В работе были использованы мышиные модели досимптомной стадии БП, поздней досимптомной и ранней симптомной (РСС) стадиями БП. Для полнотранскриптомного анализа пулов РНК тканей черной субстанции и стриатума мозга мышей использовались микрочипы MouseRef-8 v2.0 Expression BeadChip Kit («Illumina», США). Полученные данные указывают на последовательное вовлечение транскриптома в патогенез БП, а также на то, что изменения на транскриптомном уровне процессов транспорта и митохондриального биогенеза могут играть важную роль в нейродегенерации при БП уже на самых ранних этапах. Parkinson’s disease (PD) is a complex systemic disease, mainly associated with the death of dopaminergic neurons. Despite the obvious progress made in the study of molecular genetic factors and mechanisms of PD pathogenesis, it has now become clear that violations in the DNA structure do not describe the entire spectrum of pathological changes observed during the development of the disease. It has now been shown that changes at the transcriptome level can have a significant effect on the pathogenesis of PD. The authors used models of the presymptomatic stage of PD with mice decapitation after 6 hours (6 h-PSS), presymptomatic stage with decapitation after 24 hours (24 h-PSS), advanced presymptomatic (Adv-PSS) and early symptomatic (ESS) stages of PD. For whole transcriptome analysis of RNA pools of the substantia nigra and mouse striatum, the MouseRef-8 v2.0 Expression BeadChip Kit microchips (Illumina, USA) were used. As a result of the analysis of whole transcriptome data, it was shown that, there are a greater number of statistically significant changes in the tissues of the brain and peripheral blood of mice with Adv-PSS and ESS models of PD compared to 6 h-PSS and 24 h-PSS models. In general, the obtained data indicate the sequential involvement of the transcriptome in the pathogenesis of PD, as well as the fact that changes at the transcriptome level of the processes of transport and mitochondrial biogenesis can play an important role in neurodegeneration in PD at an early stage.

Liposomes: Novel Drug Delivery Approach for Targeting Parkinson’s Disease

2020 ◽  
Vol 26 (37) ◽  
pp. 4721-4737 ◽  
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem H. Pottoo ◽  
Faizana Fayaz ◽  
Anjali Sharma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Neural Cells ◽  
Blood Brain ◽  
The Brain

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.

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