L-DOPA and Serotonergic Neurons: Functional Implication and Therapeutic Perspectives in Parkinson's Disease

2011 ◽  
Vol 11 (4) ◽  
pp. 305-320 ◽  
Author(s):  
Sylvia Navailles ◽  
Manolo Carta ◽  
Martin Guthrie ◽  
Philippe De Deurwaerdere
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Serotonergic Neurons ◽  
Functional Implication

Dysfunction of serotonergic neurons in Parkinson's disease and dyskinesia

2019 ◽  
pp. 259-279 ◽  
Author(s):  
Sergio Vegas-Suarez ◽  
Elena Paredes-Rodriguez ◽  
Asier Aristieta ◽  
Jose V. Lafuente ◽  
Cristina Miguelez ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Serotonergic Neurons

scholarly journals L-DOPA in Parkinson’s Disease: Looking at the “False” Neurotransmitters and Their Meaning

2019 ◽  
Vol 21 (1) ◽  
pp. 294 ◽  
Author(s):  
Chagraoui ◽  
Boulain ◽  
Juvin ◽  
Anouar ◽  
Barrière ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mechanism Of Action ◽  
Serotonergic Neurons ◽  
Distinct Cell ◽  
Metabolic Products ◽  
Initial Hypothesis ◽  
Brain Pattern ◽  
Monoaminergic Neurons ◽  
The Brain

L-3,4-dihydroxyphenylalanine (L-DOPA) has been successfully used in the treatment of Parkinson’s disease (PD) for more than 50 years. It fulfilled the criteria to cross the blood–brain barrier and counteract the biochemical defect of dopamine (DA). It remarkably worked after some adjustments in line with the initial hypothesis, leaving a poor place to the plethora of mechanisms involving other neurotransmitters or mechanisms of action beyond newly synthesized DA itself. Yet, its mechanism of action is far from clear. It involves numerous distinct cell populations and does not mimic the mechanism of action of dopaminergic agonists. L-DOPA-derived DA is mainly released by serotonergic neurons as a false neurotransmitter, and serotonergic neurons are involved in L-DOPA-induced dyskinesia. The brain pattern and magnitude of DA extracellular levels together with this status of false neurotransmitters suggest that the striatal effects of DA via this mechanism would be minimal. Other metabolic products coming from newly formed DA or through the metabolism of L-DOPA itself could be involved. These compounds can be trace amines and derivatives. They could accumulate within the terminals of the remaining monoaminergic neurons. These “false neurotransmitters,” also known for some of them as inducing an “amphetamine-like” mechanism, could reduce the content of biogenic amines in terminals of monoaminergic neurons, thereby impairing the exocytotic process of monoamines including L-DOPA-induced DA extracellular outflow. The aim of this review is to present the mechanism of action of L-DOPA with a specific attention to “false neurotransmission.”

scholarly journals Serotonin 5-HT4 Receptor Agonists Improve Facilitation of Contextual Fear Extinction in An MPTP-Induced Mouse Model of Parkinson’s Disease

2019 ◽  
Vol 20 (21) ◽  
pp. 5340 ◽  
Author(s):  
Ishii ◽  
Kinoshita ◽  
Muroi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Adenosine Monophosphate ◽  
Fear Extinction ◽  
Gabaergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Serotonergic Neurons ◽  
Contextual Fear ◽  
Memory Extinction

Previously, we found that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) model mice (PD mice) showed facilitation of hippocampal memory extinction via reduced cyclic adenosine monophosphate (cAMP)/cAMP-dependent response element-binding protein (CREB) signaling, which may cause cognitive impairment in PD. Serotonergic neurons in the median raphe nucleus (MnRN) project to the hippocampus, and functional abnormalities have been reported. In the present study, we investigated the effects of the serotonin 5-HT4 receptor (5-HT4R) agonists prucalopride and velusetrag on the facilitation of memory extinction observed in PD mice. Both 5-HT4R agonists restored facilitation of contextual fear extinction in PD mice by stimulating the cAMP/CREB pathway in the dentate gyrus of the hippocampus. A retrograde fluorogold-tracer study showed that γ-aminobutyric acid-ergic (GABAergic) neurons in the reticular part of the substantia nigra (SNr), but not dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc), projected to serotonergic neurons in the MnRN, which are known to project their nerve terminals to the hippocampus. It is possible that the degeneration of the SNpc DAergic neurons in PD mice affects the SNr GABAergic neurons, and thereafter, the serotonergic neurons in the MnRN, resulting in hippocampal dysfunction. These findings suggest that 5HT4R agonists could be potentially useful as therapeutic drugs for treating cognitive deficits in PD.

Serotonergic neurons mediate ectopic release of dopamine induced by l-DOPA in a rat model of Parkinson's disease

2010 ◽  
Vol 38 (1) ◽  
pp. 136-143 ◽  
Author(s):  
Sylvia Navailles ◽  
Bernard Bioulac ◽  
Christian Gross ◽  
Philippe De Deurwaerdère
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Serotonergic Neurons

Evaluation of Efferent Auditory System and Hearing Quality in Parkinson's Disease: Is the Difficulty in Speech Understanding in Complex Listening Conditions Related to Neural Degeneration or Aging?

2020 ◽  
pp. 1-9
Author(s):  
Nuriye Yıldırım Gökay ◽  
Bülent Gündüz ◽  
Fatih Söke ◽  
Recep Karamert
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Auditory System ◽  
Otoacoustic Emissions ◽  
Pure Tone ◽  
Pure Tone Audiometry ◽  
Auditory Pathway ◽  
Normal Hearing ◽  
System Function ◽  
Distortion Product

Purpose The effects of neurological diseases on the auditory system have been a notable issue for investigators because the auditory pathway is closely associated with neural systems. The purposes of this study are to evaluate the efferent auditory system function and hearing quality in Parkinson's disease (PD) and to compare the findings with age-matched individuals without PD to present a perspective on aging. Method The study included 35 individuals with PD (mean age of 48.50 ± 8.00 years) and 35 normal-hearing peers (mean age of 49 ± 10 years). The following tests were administered for all participants: the first section of the Speech, Spatial and Qualities of Hearing Scale; pure-tone audiometry, speech audiometry, tympanometry, and acoustic reflexes; and distortion product otoacoustic emissions (DPOAEs) and contralateral suppression of DPOAEs. SPSS Version 25 was used for statistical analyses, and values of p < .05 were considered statistically significant. Results There were no statistically significant differences in the pure-tone audiometry thresholds and DPOAE responses between the individuals with PD and their normal-hearing peers ( p = .732). However, statistically significant differences were found between the groups in suppression levels of DPOAEs and hearing quality ( p < .05). In addition, a statistically significant and positive correlation was found between the amount of suppression at some frequencies and the Speech, Spatial and Qualities of Hearing Scale scores. Conclusions This study indicates that medial olivocochlear efferent system function and the hearing quality of individuals with PD were affected adversely due to the results of PD pathophysiology on the hearing system. For optimal intervention and follow-up, tasks related to hearing quality in daily life can also be added to therapies for PD.

Sign in / Sign up

Export Citation Format

Share Document