Correlation between changes in CSF dopamine turnover and development of dyskinesia in Parkinson's disease

Lunardi, Gianluigi; Galati, Salvatore; Tropepi, Domenicantonio; Moschella, Vincenzo; Brusa, Livia; Pierantozzi, Mariangela; Stefani, Alessandro; Rossi, Silvia; Fornai, Francesco; Fedele, Ernesto; Stanzione, Paolo; Hainsworth, Atticus H.; Pisani, Antonio

doi:10.1016/j.parkreldis.2008.10.001

Cited by 49 publications

(42 citation statements)

References 18 publications

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“…As regards CSF biomarkers, the previous study conducted in our site found altered concentrations of DA metabolites in more advanced PD stages (Lunardi et al, 2009). In that study, we demonstrated that metabolite/DA ratios, evaluated from basal CSF samples collected in off-therapy condition and after a prolonged washout, was significantly higher in advanced and dyskinetic patients compared to untreated ones.…”

Section: Accepted Manuscriptsupporting

confidence: 53%

“…Indeed, the decrease of DA levels in the CSF occurs prior to the development of dyskinesia in PD patients. Moreover, a previous report by our group documented that advanced PD patients are affected by DA metabolism dysregulation, not only by decreased DA CSF levels (Lunardi et al, 2009). In fact, the increase of DA metabolism, featured by the higher HVA/DA ratio, has been related to the occurrence of dyskinesia in advanced PD patients (Lunardi et al, 2009).…”

Section: Introductionmentioning

confidence: 76%

“…Moreover, a previous report by our group documented that advanced PD patients are affected by DA metabolism dysregulation, not only by decreased DA CSF levels (Lunardi et al, 2009). In fact, the increase of DA metabolism, featured by the higher HVA/DA ratio, has been related to the occurrence of dyskinesia in advanced PD patients (Lunardi et al, 2009). However, not only DAergic system but also serotoninergic, cholinergic, noradrenergic, opioid and other central neurotransmitter systems are impaired in PD pathology, which is actually In particular, the present study takes advantage from the un-published findings of the previous one 2).…”

Section: Introductionmentioning

confidence: 76%

“…A possible pitfall of our study regards the naturalistic design, the fact that patients were admitted on a consecutive base and, more critically, without a rather extended washout (as performed, for instance, by pivotal investigation in US or Italy, in which CSF samples had been collected following 2-5 or weeks of drug-suspension (Lewitt et al, 1992;Lunardi et al, 2009). The present washout procedure might be too short, since HVA levels might still be unpredictable or still high, despite two days washout, before the LD challenge.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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Homovanillic acid in CSF of mild stage Parkinson's disease patients correlates with motor impairment

Pierantozzi

Olivola

Galati

et al. 2017

Neurochemistry International

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In Parkinson's disease (PD), several efforts have been spent in order to find biochemical parameters able to identify the progression of the pathological processes at the basis of the disease. It is already known that advanced PD patients manifesting dyskinesia are featured by the high homovanillic acid (HVA)/dopamine (DA) ratio, suggesting the increased turnover of DA in these patients. Less clear is whether similar changes affect mild and moderate stages of the disease (between 1 and 2. The present findings showed the early alteration of the DA pre-synaptic machinery, as documented by the progressive increase of CSF HVA concentrations, which also correlated with PD motor impairment. Therefore, we suggest the potential use of measuring the CSF HVA level as a possible biomarker of PD stage changes in order to monitor the effectiveness of PD-modifying pharmacological therapies.

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Section: Accepted Manuscriptsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 76%

Section: Accepted Manuscriptmentioning

confidence: 99%

See 2 more Smart Citations

Homovanillic acid in CSF of mild stage Parkinson's disease patients correlates with motor impairment

Pierantozzi

Olivola

Galati

et al. 2017

Neurochemistry International

Self Cite

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“…The neuronal loss might also explain why we do not see an increased ratio between the dopamine metabolite HVA and the serotonin metabolite 5HIAA in CSF, as reported in children with DAT deficiency syndrome (14,15). Notably, some studies report reduced HVA levels in the CSF of Parkinson's patients (65,66), arguing that the normal, not decreased, HVA value of our patient reflects a relative increase in the accumulation and degradation of extraneuronal dopamine as compared with the putative numbers of remaining neurons. Moreover, residual activity of the DAT mutants carried by the proband would also be expected to oppose extracellular dopamine accumulation compared with patients with no DAT expression.…”

Section: Figurementioning

confidence: 55%

Missense dopamine transporter mutations associate with adult parkinsonism and ADHD

Herborg

Skjørringe²,

Yasmeen³

et al. 2014

J. Clin. Invest.

133

171

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Parkinsonism and attention deficit hyperactivity disorder (ADHD) are widespread brain disorders that involve disturbances of dopaminergic signaling. The sodium-coupled dopamine transporter (DAT) controls dopamine homeostasis, but its contribution to disease remains poorly understood. Here, we analyzed a cohort of patients with atypical movement disorder and identified 2 DAT coding variants, DAT-Ile312Phe and a presumed de novo mutant DAT-Asp421Asn, in an adult male with early-onset parkinsonism and ADHD. According to DAT single-photon emission computed tomography (DAT-SPECT) scans and a fluoro-deoxy-glucose-PET/MRI (FDG-PET/MRI) scan, the patient suffered from progressive dopaminergic neurodegeneration. In heterologous cells, both DAT variants exhibited markedly reduced dopamine uptake capacity but preserved membrane targeting, consistent with impaired catalytic activity. Computational simulations and uptake experiments suggested that the disrupted function of the DAT-Asp421Asn mutant is the result of compromised sodium binding, in agreement with Asp421 coordinating sodium at the second sodium site. For DAT-Asp421Asn, substrate efflux experiments revealed a constitutive, anomalous efflux of dopamine, and electrophysiological analyses identified a large cation leak that might further perturb dopaminergic neurotransmission. Our results link specific DAT missense mutations to neurodegenerative early-onset parkinsonism. Moreover, the neuropsychiatric comorbidity provides additional support for the idea that DAT missense mutations are an ADHD risk factor and suggests that complex DAT genotype and phenotype correlations contribute to different dopaminergic pathologies.

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Highly Deformable Double‐Sided Neural Probe with All‐in‐One Electrode System for Real‐Time In Vivo Detection of Dopamine for Parkinson's Disease

Jung,

Ha,

Park

et al. 2023

Adv Funct Materials

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Precise monitoring of neurotransmitters, such as dopamine (DA), is critical for understanding brain function and treating neurological disorders since dysregulation of DA implicates in a range of disorders, including Parkinson's disease (PD), schizophrenia, and addiction. This study proposes a multi‐deformable double‐sided (MDD) DA‐sensing probe with the three‐electrode system in all‐in‐one form for reliable real‐time monitoring of DA dynamics by integrating working, reference, and counter electrodes on a single probe. The proposed probe achieves high DA sensitivity and selectivity in virtue of enzyme immobilization on the 3D nanostructures grown on working electrode. Also, the serpentine design is employed for the electrodes to withstand in various deformations by achieving high stretchability and manage the stress induced on the probe. Experimental and computational analysis demonstrates an effective reduction in induced‐stress on the electrodes. The MDD DA‐sensing probe is implanted into the brain with success to enable real‐time, in vivo monitoring of DA levels in rodents. Furthermore, DA dynamic changes are monitored before and after treatment with L‐DOPA in hemi‐PD mice. This extremely deformable implantable probe has the potential for use in the study and treatment of neurodegenerative diseases, providing reliable monitoring of DA dynamics with minimal damage to brain tissue.

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Correlation between changes in CSF dopamine turnover and development of dyskinesia in Parkinson's disease

Cited by 49 publications

References 18 publications

Homovanillic acid in CSF of mild stage Parkinson's disease patients correlates with motor impairment

Homovanillic acid in CSF of mild stage Parkinson's disease patients correlates with motor impairment

Missense dopamine transporter mutations associate with adult parkinsonism and ADHD

Highly Deformable Double‐Sided Neural Probe with All‐in‐One Electrode System for Real‐Time In Vivo Detection of Dopamine for Parkinson's Disease

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