scholarly journals Imbalanced Dopaminergic Transmission Mediated by Serotonergic Neurons in L-DOPA-Induced Dyskinesia

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Sylvia Navailles ◽  
Philippe De Deurwaerdère
Keyword(s):  
Brain Regions ◽  
Term Treatment ◽  
Serotonergic Neurons ◽  
Brain Areas ◽  
Dopaminergic Transmission ◽  
The Core ◽  
Long Term Treatment ◽  
The Brain ◽  
Serotonergic Innervation

L-DOPA-induced dyskinesias (LIDs) are one of the main motor side effects of L-DOPA therapy in Parkinson's disease. The review will consider the biochemical evidence indicating that the serotonergic neurons are involved in the dopaminergic effects of L-DOPA in the brain. The consequences are an ectopic and aberrant release of dopamine that follows the serotonergic innervation of the brain. After mid- to long-term treatment with L-DOPA, the pattern of L-DOPA-induced dopamine release is modified. In several brain regions, its effect is dramatically reduced while, in the striatum, its effect is quite preserved. LIDs could appear when the dopaminergic effects of L-DOPA fall in brain areas such as the cortex, enhancing the subcortical impact of dopamine and promoting aberrant motor responses. The consideration of the serotonergic system in the core mechanism of action of L-DOPA opens an important reserve of possible strategies to limit LIDs.

scholarly journals Platelet counts in epileptic children receiving valproic acid

2020 ◽  
Vol 60 (1) ◽  
pp. 13-7
Author(s):  
Lilik Indrayati ◽  
Fadhilah Tia Nur ◽  
Bambang Soebagyo
Keyword(s):  
Valproic Acid ◽  
Epileptic Seizures ◽  
Term Treatment ◽  
Common Adverse Event ◽  
Platelet Counts ◽  
Central Java ◽  
Long Term Treatment ◽  
Epileptic Children ◽  
The Brain

Background Epileptic seizures are a transient occurrence resulting from abnormal, excessive, or synchronous neural activity in the brain. Epilepsy requires long-term treatment, increasingly larger doses, and combination therapy. Anti-epileptic drugs (AEDs), especially valproic acid (VPA), are the main treatment of choice. Thrombocytopenia is the most common adverse event from AEDs. Objective To evaluate platelet counts in epileptic children receiving valproic acid monotherapy vs. polytherapy. Methods This analytic, observational, retrospective cohort study was conducted in children with epilepsy below 18 years of age and treated in Dr. Moewardi Hospital, Surakarta, Central Java. Subjects had received VPA treatment for at least 6 months, either as monotherapy or polytherapy. There were 40 subjects in each group (VPA monotherapy vs. VPA polytherapy). The exclusion criteria were patients who had thrombocytopenia and did not take valproic acid regularly. The data was taken from laboratory and the outcome assessed was decreasing of platelet count. Results  Administration of VPA as monotherapy vs. polytherapy was not significantly associated with incidence of thrombocytopenia. However, duration of VPA use > 2 years was associated with significantly greater proportion of thrombocytopenia, with OR 33.0 (95%CI 4.157 to 261.962; P=0.001) compared to VPA use < 2 years. Similarly, VPA dose of >30 mg/kg/day was significantly associated with greater proportion of thrombocytopenia, with OR 4.081 (95%CI 1.337 to 12.458; P=0.013) compared to <30 mg/kg/day dosage. Conclusion Incidence of thrombocytopenia is not significantly different between VPA as a  monotherapy and polytherapy. However, higher VPA dose and longer VPA duration are associated with higher proportion of thrombocytopenia.

Long-term treatment with clonidine and α-receptors in the brain of Normotensive rats

1984 ◽  
Vol 321 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Franca Cerrito ◽  
Maria Martire ◽  
Paolo Preziosi
Keyword(s):  
Term Treatment ◽  
Long Term Treatment ◽  
The Brain

scholarly journals Circuit Mechanisms of L-DOPA-Induced Dyskinesia (LID)

2021 ◽  
Vol 15 ◽  
Author(s):  
Kai Yang ◽  
Xinyue Zhao ◽  
Changcai Wang ◽  
Cheng Zeng ◽  
Yan Luo ◽  
...  
Keyword(s):  
Firing Rate ◽  
Firing Pattern ◽  
Theoretical Models ◽  
Brain Regions ◽  
Term Treatment ◽  
Ensemble Model ◽  
Rate Model ◽  
Multisystem Disease ◽  
Long Term Treatment

L-DOPA is the criterion standard of treatment for Parkinson disease. Although it alleviates some of the Parkinsonian symptoms, long-term treatment induces L-DOPA–induced dyskinesia (LID). Several theoretical models including the firing rate model, the firing pattern model, and the ensemble model are proposed to explain the mechanisms of LID. The “firing rate model” proposes that decreasing the mean firing rates of the output nuclei of basal ganglia (BG) including the globus pallidus internal segment and substantia nigra reticulata, along the BG pathways, induces dyskinesia. The “firing pattern model” claimed that abnormal firing pattern of a single unit activity and local field potentials may disturb the information processing in the BG, resulting in dyskinesia. The “ensemble model” described that dyskinesia symptoms might represent a distributed impairment involving many brain regions, but the number of activated neurons in the striatum correlated most strongly with dyskinesia severity. Extensive evidence for circuit mechanisms in driving LID symptoms has also been presented. LID is a multisystem disease that affects wide areas of the brain. Brain regions including the striatum, the pallidal–subthalamic network, the motor cortex, the thalamus, and the cerebellum are all involved in the pathophysiology of LID. In addition, although both amantadine and deep brain stimulation help reduce LID, these approaches have complications that limit their wide use, and a novel antidyskinetic drug is strongly needed; these require us to understand the circuit mechanism of LID more deeply.

scholarly journals Escitalopram as a modulator of proopiomelanocortin, kisspeptin, Kiss1R and MCHR1 gene expressions in the male rat brain

2020 ◽  
Vol 47 (10) ◽  
pp. 8273-8278
Author(s):  
Artur Pałasz ◽  
Aneta Piwowarczyk-Nowak ◽  
Aleksandra Suszka-Świtek ◽  
Katarzyna Bogus ◽  
Łukasz Filipczyk ◽  
...  
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Mrna Level ◽  
Brain Structures ◽  
Brain Regions ◽  
Term Treatment ◽  
Male Rat ◽  
Gene Expressions ◽  
Long Term Treatment ◽  
Effect Of Treatment

Abstract Neuropeptides are important, multifunctional regulatory factors of the nervous system, being considered as a novel, atypical sites of antidepressants action. It has already been proven that some of them, such as selective serotonin reuptake inhibitors (SSRI), are able to affect peptidergic pathways in various brain regions. Despite these reports, there is so far no reports regarding the effect of treatment with SSRIs on brain proopiomelanocortin (POMC), kisspeptin, Kiss1R and MCHR1 gene expression. In the current study we examined POMC, kisspeptin, Kiss1R and MCHR1 mRNA expression in the selected brain structures (hypothalamus, hippocampus, amygdala, striatum, cerebellum and brainstem) of rats chronically treated with a 10 mg/kg dose of escitalopram using quantitative Real-Time PCR. Long-term treatment with escitalopram led to the upregulation of MCHR1 expression in the rat amygdala. Kisspeptin mRNA level was also increased in the amygdala, but Kiss1R mRNA expressions were elevated in the hippocampus, hypothalamus and cerebellum. POMC mRNA expressions were in turn decreased in the hippocampus, amygdala, cerebellum and brainstem. These results may support the hypothesis that these neuropeptides may be involved in the site-dependent actions of SSRI antidepressants. This is the first report of the effects of escitalopram on POMC, kisspeptin, Kiss1R and MCHR1 in animal brain. Our findings shed a new light on the pharmacology of SSRIs and may contribute to a better understanding of the alternative, neuropeptide-dependent modes of antidepressant action.

scholarly journals Long-Term Treatment of Cuban Policosanol Attenuates Abnormal Oxidative Stress and Inflammatory Response via Amyloid Plaques Reduction in 5xFAD Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1321
Author(s):  
Jin-Ho Kim ◽  
Dong-Kyun Lim ◽  
Yoo-Hun Suh ◽  
Keun-A Chang
Keyword(s):  
Neurodegenerative Disorder ◽  
Lipid Peroxide ◽  
Amyloid Plaques ◽  
Term Treatment ◽  
Number Of Patients ◽  
Tnf Α ◽  
Long Term Treatment ◽  
5Xfad Mice ◽  
The Brain

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder resulting in cognitive decline or dementia, the number of patients with AD is continuously increasing. Although a lot of great progress has been made in research and development of AD therapeutics, there is no fundamental cure for this disease yet. This study demonstrated the memory-improving effects of Cuban policosanol (PCO) in 5xFAD mice, which is an animal model of AD. Following 4-months of treatment with PCO in 5xFAD mice, we found that the number of amyloid plaques decreased in the brain compared to the vehicle-treated 5xFAD mice. Long-term PCO treatment in 5xFAD mice resulted in the reduction of gliosis and abnormal inflammatory cytokines level (interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF]-α) in the cortex and hippocampus. Levels of lipid peroxide (4-hydroxynonenal [4-HNE]) and superoxide dismutase (SOD1 and SOD2) levels were also recoverd in the brains of PCO-treated 5xFAD mice. Notably, PCO administration reduced memory deficits in the passive avoidance test, as well as synaptic loss (PSD-95, synaptophysin) in 5xFAD mice. Collectively, we identified the potential effects of PCO as a useful supplement to delay or prevent AD progression by inhibiting the formation of Aβ plaques in the brain.

scholarly journals Long-Term Intranasal Insulin Aspart: A Profile of Gene Expression, Memory, and Insulin Receptors in Aged F344 Rats

2019 ◽  
Vol 75 (6) ◽  
pp. 1021-1030 ◽  
Author(s):  
Hilaree N Frazier ◽  
Adam O Ghoweri ◽  
Emily Sudkamp ◽  
Eleanor S Johnson ◽  
Katie L Anderson ◽  
...  
Keyword(s):  
Insulin Aspart ◽  
Insulin Receptors ◽  
Term Treatment ◽  
Intranasal Insulin ◽  
Morris Water Maze Task ◽  
Long Term Treatment ◽  
Microarray Analyses ◽  
The Impact ◽  
The Brain

Abstract Intranasal insulin is a safe and effective method for ameliorating memory deficits associated with pathological brain aging. However, the impact of different formulations and the duration of treatment on insulin’s efficacy and the cellular processes targeted by the treatment remain unclear. Here, we tested whether intranasal insulin aspart, a short-acting insulin formulation, could alleviate memory decline associated with aging and whether long-term treatment affected regulation of insulin receptors and other potential targets. Outcome variables included measures of spatial learning and memory, autoradiography and immunohistochemistry of the insulin receptor, and hippocampal microarray analyses. Aged Fischer 344 rats receiving long-term (3 months) intranasal insulin did not show significant memory enhancement on the Morris water maze task. Autoradiography results showed that long-term treatment reduced insulin binding in the thalamus but not the hippocampus. Results from hippocampal immunofluorescence revealed age-related decreases in insulin immunoreactivity that were partially offset by intranasal administration. Microarray analyses highlighted numerous insulin-sensitive genes, suggesting insulin aspart was able to enter the brain and alter hippocampal RNA expression patterns including those associated with tumor suppression. Our work provides insights into potential mechanisms of intranasal insulin and insulin resistance, and highlights the importance of treatment duration and the brain regions targeted.

The Safety of Fluoxetine - An Update

1988 ◽  
Vol 153 (S3) ◽  
pp. 77-86 ◽  
Author(s):  
Glenn L. Cooper
Keyword(s):  
Tricyclic Antidepressants ◽  
Term Treatment ◽  
Major Depressive ◽  
Serious Adverse Events ◽  
Double Blind ◽  
The Core ◽  
Antidepressant Agent ◽  
Long Term Treatment ◽  
One Year

Fluoxetine is a new antidepressant agent which is a selective inhibitor of neuronal serotonin uptake; it has minimal affinity for muscarinic, dopaminergic, histaminic, serotonergic, or noradrenergic receptors (Stark et al, 1985). This specificity of activity suggests that fluoxetine may have a side-effect profile which is different from previously available antidepressants.The safety of fluoxetine has been extensively studied: several hundred patients have received the drug continuously for more than one year - some have had therapy for 5 years or more. Previous reviews of the safety of fluoxetine (Wernicke, 1985; Zerbe, 1986) have described a smaller population of patients than is now available.This review is drawn from data pooled from comparative clinical trials, which included 4336 patients: fluoxetine - 2938, tricyclic antidepressants (TCAs) - 599, and placebo - 799 patients. The TCAs studied were amitriptyline, imipramine, and doxepin. Most patients were adults with major depressive disorder, and the most common study design was a 6-week comparative double-blind phase, followed by unblinded long-term treatment. While the core of this study is a data base of 2938 fluoxetine-treated patients, all serious adverse events reported in over 7500 fluoxetine-treated patients worldwide, as of mid-1987, have been included.

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