scholarly journals Cardiac Tyrosine Hydroxylase Activation and Mb-Comt in Dyskinetic Monkeys

2021 ◽  
Author(s):  
Lorena Cuenca-Bermejo ◽  
Pilar Almela ◽  
Pablo Gallo-Soljancic ◽  
José Yuste ◽  
Vicente de Pablos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Tyrosine Hydroxylase ◽  
Dopaminergic System ◽  
Nigrostriatal Pathway ◽  
Noradrenergic Neurons ◽  
Methyl Transferase ◽  
Mptp Treatment ◽  
The Impact

Abstract The impact of age-associated disorders is increasing as the life expectancy of the population increments. Cardiovascular diseases and neurodegenerative disorders, such as Parkinson’s disease, have the highest social and economic burden and increasing evidence show interrelations between them. Particularly, dysfunction of the cardiovascular nervous system is part of the dysautonomic symptoms of Parkinson’s disease, although more studies are needed to elucidate the role of cardiac function on it. We analyzed the dopaminergic system in the nigrostriatal pathway of Parkinsonian and dyskinetic monkeys and the expression of some key proteins in the metabolism and synthesis of catecholamines in the heart: total and phosphorylated (phospho) tyrosine hydroxylase (TH), and membrane (MB) and soluble (S) isoforms of catechol-O-methyl transferase (COMT). The dopaminergic system was significantly depleted in all MPTP-intoxicated monkeys. MPTP- and MPTP+L-DOPA-treated animals also showed a decrease in total TH expression in both right (RV) and left ventricle (LV). We found a significant increase of phospho-TH in both groups (MPTP and MPTP+L-DOPA) in the LV, while this increase was only observed in MPTP-treated monkeys in the RV. MB-COMT analysis showed a very significant increase of this isoform in the LV of MPTP- and MPTP+L-DOPA-treated animals, with no significant differences in S-COMT levels. These data suggest that MB-COMT is the main isoform implicated in the cardiac noradrenergic changes observed after MPTP treatment, suggesting an increase in NA metabolism. Moreover, the increase of TH activity indicates that cardiac noradrenergic neurons still respond despite MPTP treatment.

scholarly journals Cardiac tyrosine hydroxylase activation and MB-COMT in dyskinetic monkeys

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lorena Cuenca-Bermejo ◽  
Pilar Almela ◽  
Pablo Gallo-Soljancic ◽  
José E. Yuste ◽  
Vicente de Pablos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Tyrosine Hydroxylase ◽  
Dopaminergic System ◽  
Nigrostriatal Pathway ◽  
Noradrenergic Neurons ◽  
Methyl Transferase ◽  
Mptp Treatment ◽  
The Impact

AbstractThe impact of age-associated disorders is increasing as the life expectancy of the population increments. Cardiovascular diseases and neurodegenerative disorders, such as Parkinson’s disease, have the highest social and economic burden and increasing evidence show interrelations between them. Particularly, dysfunction of the cardiovascular nervous system is part of the dysautonomic symptoms of Parkinson’s disease, although more studies are needed to elucidate the role of cardiac function on it. We analyzed the dopaminergic system in the nigrostriatal pathway of Parkinsonian and dyskinetic monkeys and the expression of some key proteins in the metabolism and synthesis of catecholamines in the heart: total and phosphorylated (phospho) tyrosine hydroxylase (TH), and membrane (MB) and soluble (S) isoforms of catechol-O-methyl transferase (COMT). The dopaminergic system was significantly depleted in all MPTP-intoxicated monkeys. MPTP- and MPTP + L-DOPA-treated animals also showed a decrease in total TH expression in both right (RV) and left ventricle (LV). We found a significant increase of phospho-TH in both groups (MPTP and MPTP + L-DOPA) in the LV, while this increase was only observed in MPTP-treated monkeys in the RV. MB-COMT analysis showed a very significant increase of this isoform in the LV of MPTP- and MPTP + L-DOPA-treated animals, with no significant differences in S-COMT levels. These data suggest that MB-COMT is the main isoform implicated in the cardiac noradrenergic changes observed after MPTP treatment, suggesting an increase in noradrenaline (NA) metabolism. Moreover, the increase of TH activity indicates that cardiac noradrenergic neurons still respond despite MPTP treatment.

scholarly journals Cardiac Tyrosine Hydroxylase Activation and MB-COMT in Dyskinetic Monkeys 

2020 ◽  
Author(s):  
Lorena Cuenca-Bermejo ◽  
Pilar Almela ◽  
Pablo Gallo-Soljancic ◽  
Jose E. Yuste ◽  
Vicente de Pablos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Tyrosine Hydroxylase ◽  
Substantia Nigra Pars Compacta ◽  
Nigrostriatal Pathway ◽  
Methyl Transferase ◽  
Catecholaminergic System ◽  
Mptp Treatment ◽  
The Impact

Abstract Background: The impact of age-associated disorders is increasing as the life expectancy of the population increments. Cardiovascular diseases and neurodegenerative disorders, such as Parkinson’s disease, have the highest social and economic burden and increasing evidence show interrelations between them. Particularly, dysfunction of the cardiovascular nervous system is part of the dysautonomic symptoms of Parkinson’s disease, although more studies are needed to elucidate the role of cardiac function on it . Methods: We analyzed the dopaminergic system in the nigrostriatal pathway of Parkinsonian and dyskinetic monkeys and the expression of some key proteins in the metabolism and synthesis of catecholamines in the heart: total and phosphorylated (phospho) tyrosine hydroxylase (TH), and membrane (MB) and soluble (S) isoforms of catechol-O-methyl transferase (COMT). Results: The number of dopaminergic neurons in the Substantia Nigra pars compacta and the optical density of TH+ fibers and dopamine transporter in the striatum were significantly decreased in all MPTP-intoxicated monkeys. MPTP- and MPTP+L-DOPA-treated animals also showed a decrease in total TH expression in both right (RV) and left ventricle (LV). We found a significant increase of phospho-TH in both groups (MPTP and MPTP+L-DOPA) in the LV, while this increase was only observed in MPTP-treated monkeys in the RV. MB-COMT analysis showed a very significant increase of this isoform in the LV of MPTP- and MPTP+L-DOPA-treated animals. However, we found no significant differences in S-COMT levels. These data suggest that MB-COMT is the main isoform implicated in the cardiac noradrenergic changes observed after MPTP treatment, suggesting an increase in NA metabolism. Moreover, the increase of TH activity indicates that cardiac noradrenergic neurons still respond despite MPTP treatment. Conclusions: These results could help to elucidate the possible role of alterations in the catecholaminergic system that can contribute to noradrenergic deficiency in the hearts of PD patients. Therefore, this information might be relevant to clinical field, contributing to the therapeutic design of the disease.

scholarly journals A selective effect of dopamine on information-seeking

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Valentina Vellani ◽  
Lianne P de Vries ◽  
Anne Gaule ◽  
Tali Sharot
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Information Seeking ◽  
Selective Effect ◽  
Reward Seeking ◽  
The Impact ◽  
The Brain ◽  
Insight Into ◽  
Primary Reward

Humans are motivated to seek information from their environment. How the brain motivates this behavior is unknown. One speculation is that the brain employs neuromodulatory systems implicated in primary reward-seeking, in particular dopamine, to instruct information-seeking. However, there has been no causal test for the role of dopamine in information-seeking. Here, we show that administration of a drug that enhances dopamine function (dihydroxy-L-phenylalanine; L-DOPA) reduces the impact of valence on information-seeking. Specifically, while participants under Placebo sought more information about potential gains than losses, under L-DOPA this difference was not observed. The results provide new insight into the neurobiology of information-seeking and generates the prediction that abnormal dopaminergic function (such as in Parkinson’s disease) will result in valence-dependent changes to information-seeking.

scholarly journals Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease

2020 ◽  
Vol 21 (10) ◽  
pp. 3459 ◽  
Author(s):  
Sandra Barata-Antunes ◽  
Fábio G. Teixeira ◽  
Bárbara Mendes-Pinheiro ◽  
Ana V. Domingues ◽  
Helena Vilaça-Faria ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Welfare ◽  
Neurodegenerative Disorder ◽  
Negative Impact ◽  
Substantia Nigra Pars Compacta ◽  
Nigrostriatal Pathway ◽  
Aged Rats ◽  
Age Related ◽  
The Impact

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. The neurodegeneration leading to incapacitating motor abnormalities mainly occurs in the nigrostriatal pathway due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several animal models have been developed not only to better understand the mechanisms underlying neurodegeneration but also to test the potential of emerging disease-modifying therapies. However, despite aging being the main risk factor for developing idiopathic PD, most of the studies do not use aged animals. Therefore, this study aimed at assessing the effect of aging in the unilateral 6-hydroxydopamine (6-OHDA)-induced animal model of PD. For this, female young adult and aged rats received a unilateral injection of 6-OHDA into the medial forebrain bundle. Subsequently, the impact of aging on 6-OHDA-induced effects on animal welfare, motor performance, and nigrostriatal integrity were assessed. The results showed that aging had a negative impact on animal welfare after surgery. Furthermore, 6-OHDA-induced impairments on skilled motor function were significantly higher in aged rats when compared with their younger counterparts. Nigrostriatal histological analysis further revealed an increased 6-OHDA-induced dopaminergic cell loss in the SNpc of aged animals when compared to young animals. Overall, our results demonstrate a higher susceptibility of aged animals to 6-OHDA toxic insult.

Pyrethroid and organophosphate insecticide exposure in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease: an immunohistochemical analysis of tyrosine hydroxylase and glial fibrillary acidic protein in dorsolateral striatum

2009 ◽  
Vol 25 (1) ◽  
pp. 25-39 ◽  
Author(s):  
CA Dodd ◽  
BG Klein
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Tyrosine Hydroxylase ◽  
Mouse Model ◽  
Glial Fibrillary Acidic Protein ◽  
Immunohistochemical Analysis ◽  
Acidic Protein ◽  
Nigrostriatal Pathway ◽  
Organophosphate Insecticide ◽  
Nigrostriatal Degeneration

The pyrethroid insecticide permethrin and the organophosphate insecticide chlorpyrifos can experimentally produce Parkinson’s disease (PD)-associated changes in the dopaminergic nigrostriatal pathway, short of frank degeneration, although at doses considerably higher than from a likely environmental exposure. The ability of permethrin (200 mg/kg), chlorpyrifos (50 mg/kg), or combined permethrin + chlorpyrifos to facilitate nigrostriatal damage in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg) C57BL/6 mouse model of PD was investigated in three separate experiments. Tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) immunohistochemistry assessed nigrostriatal degeneration or nigrostriatal damage more subtle than frank degeneration. Four fields in the dorsolateral caudate-putamen were examined at two rostrocaudal locations. The dopaminergic neurotoxin MPTP decreased striatal TH immunopositive neuropil and increased GFAP immunopositive neuropil. Neither permethrin nor chlorpyrifos, alone or in combination, altered the effects of MPTP upon TH or GFAP immunostaining. Permethrin alone increased striatal GFAP immunopositive neuropil but not when combined with chlorpyrifos treatment. Therefore, combined administration of the two insecticides appeared to protect against an increase in a neuropathological indicator of striatal damage seen with permethrin treatment alone. Differences compared with analysis of entire striatum emphasize the value of varying the topographic focus used to assess nigrostriatal degeneration in studies of insecticides in PD.

scholarly journals Astrocytic Oxidative/Nitrosative Stress Contributes to Parkinson’s Disease Pathogenesis: The Dual Role of Reactive Astrocytes

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 265 ◽  
Author(s):  
Asha Rizor ◽  
Edward Pajarillo ◽  
James Johnson ◽  
Michael Aschner ◽  
Eunsook Lee
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nitrosative Stress ◽  
Critical Role ◽  
Substantia Nigra Pars Compacta ◽  
Environmental Toxicants ◽  
Oxidative And Nitrosative Stress ◽  
Reactive Astrogliosis ◽  
The Impact

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide; it is characterized by dopaminergic neurodegeneration in the substantia nigra pars compacta, but its etiology is not fully understood. Astrocytes, a class of glial cells in the central nervous system (CNS), provide critical structural and metabolic support to neurons, but growing evidence reveals that astrocytic oxidative and nitrosative stress contributes to PD pathogenesis. As astrocytes play a critical role in the production of antioxidants and the detoxification of reactive oxygen and nitrogen species (ROS/RNS), astrocytic oxidative/nitrosative stress has emerged as a critical mediator of the etiology of PD. Cellular stress and inflammation induce reactive astrogliosis, which initiates the production of astrocytic ROS/RNS and may lead to oxidative/nitrosative stress and PD pathogenesis. Although the cause of aberrant reactive astrogliosis is unknown, gene mutations and environmental toxicants may also contribute to astrocytic oxidative/nitrosative stress. In this review, we briefly discuss the physiological functions of astrocytes and the role of astrocytic oxidative/nitrosative stress in PD pathogenesis. Additionally, we examine the impact of PD-related genes such as α-synuclein, protein deglycase DJ-1( DJ-1), Parkin, and PTEN-induced kinase 1 (PINK1) on astrocytic function, and highlight the impact of environmental toxicants, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, manganese, and paraquat, on astrocytic oxidative/nitrosative stress in experimental models.

scholarly journals A Synopsis on the Role of Tyrosine Hydroxylase in Parkinson’s Disease

2012 ◽  
Vol 11 (4) ◽  
pp. 395-409 ◽  
Author(s):  
Shams Tabrez ◽  
Nasimudeen R. Jabir ◽  
Shazi Shakil ◽  
Nigel H. Greig ◽  
Qamre Alam ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Tyrosine Hydroxylase

scholarly journals Monoamine Reuptake Inhibitors in Parkinson’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-71 ◽  
Author(s):  
Philippe Huot ◽  
Susan H. Fox ◽  
Jonathan M. Brotchie
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic System ◽  
Therapeutic Agents ◽  
Review Article ◽  
Monoamine Transporters ◽  
Noradrenergic Neurons ◽  
The Brain ◽  
Selective Dopamine ◽  
Monoamine Reuptake Inhibitors

The motor manifestations of Parkinson’s disease (PD) are secondary to a dopamine deficiency in the striatum. However, the degenerative process in PD is not limited to the dopaminergic system and also affects serotonergic and noradrenergic neurons. Because they can increase monoamine levels throughout the brain, monoamine reuptake inhibitors (MAUIs) represent potential therapeutic agents in PD. However, they are seldom used in clinical practice other than as antidepressants and wake-promoting agents. This review article summarises all of the available literature on use of 50 MAUIs in PD. The compounds are divided according to their relative potency for each of the monoamine transporters. Despite wide discrepancy in the methodology of the studies reviewed, the following conclusions can be drawn: (1) selective serotonin transporter (SERT), selective noradrenaline transporter (NET), and dual SERT/NET inhibitors are effective against PD depression; (2) selective dopamine transporter (DAT) and dual DAT/NET inhibitors exert an anti-Parkinsonian effect when administered as monotherapy but do not enhance the anti-Parkinsonian actions of L-3,4-dihydroxyphenylalanine (L-DOPA); (3) dual DAT/SERT inhibitors might enhance the anti-Parkinsonian actions of L-DOPA without worsening dyskinesia; (4) triple DAT/NET/SERT inhibitors might exert an anti-Parkinsonian action as monotherapy and might enhance the anti-Parkinsonian effects of L-DOPA, though at the expense of worsening dyskinesia.

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