Hermann (Hugh) Blaschko (1900–1993): His fundamental contributions to biochemical pharmacology and clinical medicine

2019 ◽  
Vol 27 (3) ◽  
pp. 179-183
Author(s):  
Ronald P Rubin
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Transmission ◽  
Clinical Medicine ◽  
Sympathetic Nerves ◽  
Biochemical Pharmacology

Hermann (Hugh) Blaschko was a biochemical pharmacologist best known for discovering how adrenaline (epinephrine), noradrenaline (norepinephrine), and dopamine were synthesized, stored, and metabolized in adrenomedullary cells and sympathetic nerves. Blaschko’s work not only supported the validity of the concept of neurochemical synaptic transmission but he also made fundamental contributions to the development of drugs used in clinical medicine to treat diseases such as depression, hypertension, and Parkinson's Disease.

Actions of Adenosine A2A Receptors on Synaptic Connections of Spiny Projection Neurons in the Neostriatal Inhibitory Network

2008 ◽  
Vol 99 (4) ◽  
pp. 1884-1889 ◽  
Author(s):  
Tomomi Shindou ◽  
Gordon W. Arbuthnott ◽  
Jeffery R. Wickens
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Transmission ◽  
Projection Neurons ◽  
Synaptic Connections ◽  
Adenosine A2a Receptors ◽  
A2a Receptors ◽  
Cells Of Origin ◽  
Adenosine A2a ◽  
Whole Cell Recordings

There is growing evidence that adenosine plays a crucial role in basal ganglia function, particularly in the modulation of voluntary movement. An adenosine-based treatment for Parkinson's disease shows promise in recent clinical studies. Adenosine A2A receptors, the receptors involved in this treatment, are highly expressed in the neostriatum. Previous studies have suggested opposing actions of these receptors on synaptic transmission at striatal and pallidal terminals of the same spiny projection neurons, but the cells of origin of the intrastriatal terminals mediating these actions have not been identified. We used dual whole cell recordings to record simultaneously from pairs of striatal cells; this enabled definitive identification of the presynaptic and postsynaptic cells mediating the effects of A2A receptors. We found that A2A receptors facilitate GABAergic synaptic transmission by intrastriatal collaterals of the spiny projection neurons, consistent with their previously reported actions on synaptic transmission at pallidal terminals. This neuromodulatory action on lateral inhibition in the striatum may underlie, in part, the therapeutic efficacy of adenosine-based treatments for Parkinson's disease.

Adreno-medullary sympathetic nerves and ascending baroreceptor pathways are not affected in Parkinson's disease patients with orthostatic hypotension

2012 ◽  
Vol 171 (1-2) ◽  
pp. 89
Author(s):  
Toshimasa Yamamoto ◽  
Akifumi Miyake ◽  
Toshinori Kimura ◽  
Yasuko Ohe ◽  
Naotoshi Tamura ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Orthostatic Hypotension ◽  
Sympathetic Nerves

scholarly journals Prediction of Parkinson’s Disease at Early Stage using Big Data Analytics

2020 ◽  
Vol 9 (4) ◽  
pp. 2453-2459
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Big Data ◽  
Data Analytics ◽  
Clinical Medicine ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Big Data Analytics ◽  
Analytical Techniques ◽  
Predictive Methods

Due to technological improvements in healthcare industry and clinical medicine, it requires to adapt new software techniques and tools to predict, diagnose and analyze disease patterns for making decisions in the early stage of disease. Parkinson’s disease is a neurodegenerative disorder. The PD damage the motor skills and may create speech problem and also affect the decision making process. Many people suffers with PD all over the world from many years. Day by day, the PD data has been increased, so the existing data mining predictive methods and tools does not give accurate results early for making decisions by doctors to save and increase the patient life period. Early PD symptoms can be detected by Big Data Analytics and proper medicine will be provided at the right time. In this paper, we are doing survey of predictive methods, Big Data Analytical techniques and also earlier researchers results presented.

scholarly journals Altered pallido-pallidal synaptic transmission leads to aberrant firing of globus pallidus neurons in a rat model of Parkinson's disease

2012 ◽  
Vol 590 (22) ◽  
pp. 5861-5875 ◽  
Author(s):  
Cristina Miguelez ◽  
Stéphanie Morin ◽  
Audrey Martinez ◽  
Michel Goillandeau ◽  
Erwan Bezard ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Transmission ◽  
Globus Pallidus ◽  
Rat Model

scholarly journals Effects of L-3,4-dihydroxyphenylalanine (L-Dopa) Treatment in the Neuroendocrine Response to Stress

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A67-A68
Author(s):  
Santiago Jordi Orrillo ◽  
Mercedes Imsen ◽  
Alfonsina Lizarraga ◽  
Ana Clara Romero ◽  
Fernanda De Fino ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Stress Response ◽  
Hpa Axis ◽  
Sympathetic Nerves ◽  
Serum Levels ◽  
Male Wistar Rats ◽  
Response To Stress ◽  
Behavioural Tests ◽  
Hpa Axis Activity

Abstract Stressful stimuli evoke a complex response mediated by two systems: the Sympathetic-Adreno-Medullar (SAM) axis and the Hypothalamus-Pituitary-Adrenal (HPA) axis. Among the factors involved in stress, glucocorticoids and catecholamines secreted from the adrenal glands and sympathetic nerves are the main effectors of the physiological adaptations to stressors. Besides these, prolactin (PRL) is another hormone secreted under stress conditions. Catecholamines are synthesized from the hydroxylated precursor L-Dopa. This agent is commonly used for the treatment of Parkinson’s disease and it would act as a neurotransmitter per se. On the other hand, it has been suggested that HPA axis dysregulation is a potential risk factor for the development of depression. In line with this, several studies reported that L-Dopa treatment may alter the serum levels of ACTH, PRL, and glucocorticoids in parkinsonian patients and Parkinson’s disease animal models. In the present study, we determined whether the chronic treatment with L-Dopa altered the stress response inducing depressive-like behaviours. Adult male Wistar rats were treated orally during 24 days with LEBOCAR® - commercial formulation of L-Dopa (75 mg/day) and Carbidopa (7.5 mg/day) - in drinking water. Animals were stressed by immobilization during the last 9 days of treatment and depressive-like behaviours were assessed by the sucrose intake and forced swimming tests. Behavioural tests showed no signs of depressive-like behaviours in the LEBOCAR®-treated and/or stressed rats. We next explored the SAM axis reactivity. Circulating noradrenaline and adrenaline increased in rats treated with LEBOCAR® (p<0.05; HPLC). Also, the adrenals from stressed animals showed higher content of adrenaline (p<0.05). Then, we studied the HPA axis activity. Chronically stressed rats displayed a lower ACTH secretion (ELISA) and a downregulation of POMC expression (qPCR) in the anterior pituitary (p<0.05). In addition, LEBOCAR® treatment induced a reduction in serum ACTH and POMC levels (p<0.05). As expected, serum corticosterone (ELISA) enhanced under chronic stress, an effect that was inhibited by treatment with LEBOCAR® (p<0.05). Finally, pituitary PRL gene expression (qPCR) was downregulated by LEBOCAR® treatment with a more pronounced effect when rats were also stressed (p<0.05). Our results suggest that L-Dopa alters the neuroendocrine stress response enhancing SAM axis reactivity and reducing HPA axis activity and PRL expression.

Role of cardiac sympathetic nerves in preventing orthostatic hypotension in Parkinson's disease

2014 ◽  
Vol 20 (4) ◽  
pp. 409-414 ◽  
Author(s):  
Tomohiko Nakamura ◽  
Masaaki Hirayama ◽  
Takashi Hara ◽  
Yasuaki Mizutani ◽  
Junichiro Suzuki ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Orthostatic Hypotension ◽  
Sympathetic Nerves

scholarly journals Is Chelation Therapy a Potential Treatment for Parkinson’s Disease?

2021 ◽  
Vol 22 (7) ◽  
pp. 3338
Author(s):  
Roberta J. Ward ◽  
David T. Dexter ◽  
Antonio Martin-Bastida ◽  
Robert R. Crichton
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Chelation Therapy ◽  
Clinical Medicine ◽  
Iron Chelator ◽  
Brain Regions ◽  
Iron Loading ◽  
Glia Cells ◽  
Anaemia Of Chronic Disease ◽  
Inflammatory Drugs

Iron loading in some brain regions occurs in Parkinson’s Disease (PD), and it has been considered that its removal by iron chelators could be an appropriate therapeutic approach. Since neuroinflammation with microgliosis is also a common feature of PD, it is possible that iron is sequestered within cells as a result of the “anaemia of chronic disease” and remains unavailable to the chelator. In this review, the extent of neuroinflammation in PD is discussed together with the role played by glia cells, specifically microglia and astrocytes, in controlling iron metabolism during inflammation, together with the results of MRI studies. The current use of chelators in clinical medicine is presented together with a discussion of two clinical trials of PD patients where an iron chelator was administered and showed encouraging results. It is proposed that the use of anti-inflammatory drugs combined with an iron chelator might be a better approach to increase chelator efficacy.

scholarly journals Parkinson’s disease-linked Parkin mutations impair glutamatergic synaptic transmission and plasticity

2018 ◽  
Author(s):  
Mei Zhu ◽  
Giuseppe P. Cortese ◽  
Clarissa L. Waites
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Transmission ◽  
Ampa Receptor ◽  
Hippocampal Neurons ◽  
Receptor Trafficking ◽  
Synaptic Function ◽  
Glutamatergic Synaptic Transmission ◽  
The Impact ◽  
Ampa Receptor Trafficking

AbstractParkinson’s disease (PD)-associated E3 ubiquitin ligase Parkin is enriched at glutamatergic synapses, where it ubiquitinates multiple substrates, suggesting that its mutation/loss-of-function could contribute to the etiology of PD by disrupting excitatory neurotransmission. Here, we evaluate the impact of four common PD-associated Parkin point mutations (T240M, R275W, R334C, G430D) on glutamatergic synaptic function in hippocampal neurons. We find that expression of these point mutants in Parkin-deficient and -null backgrounds alters NMDA and AMPA receptor-mediated currents and cell-surface levels, and prevents the induction of long-term depression. Mechanistically, we demonstrate that Parkin regulates NMDA receptor trafficking through its ubiquitination of GluN1, and that all four mutants are impaired in this ubiquitinating activity. Furthermore, Parkin regulates synaptic AMPA receptor trafficking via its binding and retention of the postsynaptic scaffold Homer1, and all mutants are similarly impaired in this capacity. Our findings demonstrate that pathogenic Parkin mutations disrupt glutamatergic synaptic transmission and plasticity by impeding NMDA and AMPA receptor trafficking, and through these effects likely contribute to the pathophysiology of PD inPARK2patients.

scholarly journals Synaptic potentiation of anterior cingulate cortex contributes to chronic pain of Parkinson’s disease

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Zhaoxiang Zhou ◽  
Penghai Ye ◽  
Xu-Hui Li ◽  
Yuxiang Zhang ◽  
Muhang Li ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Chronic Pain ◽  
Parkinson's Disease ◽  
Synaptic Transmission ◽  
Anterior Cingulate Cortex ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Mechanical Hypersensitivity ◽  
Mptp Treatment ◽  
Emotional Changes

AbstractParkinson’s disease (PD) is a multi-system neurodegenerative disorder. Patients with PD often suffer chronic pain. In the present study, we investigated motor, sensory and emotional changes in three different PD mice models. We found that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treatment caused significant changes in all measurements. Mechanical hypersensitivity of PD model induced by MPTP peaked at 3 days and persisted for at least 14 days. Using Fos transgenic mice, we found that neurons in the anterior cingulate cortex (ACC) were activated after MPTP treatment. Inhibiting ACC by bilateral microinjection of muscimol significantly reduced mechanical hypersensitivity and anxiety-like responses. By contrast, MPTP induced motor deficit was not affected, indicating ACC activity is mostly responsible for sensory and emotional changes. We also investigated excitatory synaptic transmission and plasticity using brain slices of MPTP treated animals. While L-LTP was blocked or significantly reduced. E-LTP was not significantly affected in slices of MPTP treated animals. LTD induced by repetitive stimulation was not affected. Furthermore, we found that paired-pulse facilitation and spontaneous release of glutamate were also altered in MPTP treated animals, suggesting presynaptic enhancement of excitatory transmission in PD. Our results suggest that ACC synaptic transmission is enhanced in the animal model of PD, and cortical excitation may play important roles in PD related pain and anxiety.

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