scholarly journals Differential Effects of Dopaminergic Therapies on Dorsal and Ventral Striatum in Parkinson's Disease: Implications for Cognitive Function

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Penny A. MacDonald ◽  
Oury Monchi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Function ◽  
Substantia Nigra ◽  
Ventral Striatum ◽  
Functional Neuroimaging ◽  
Dorsal Striatum ◽  
Cell Loss ◽  
Motor Symptoms ◽  
Dopaminergic Therapy

Cognitive abnormalities are a feature of Parkinson's disease (PD). Unlike motor symptoms that are clearly improved by dopaminergic therapy, the effect of dopamine replacement on cognition seems paradoxical. Some cognitive functions are improved whereas others are unaltered or even hindered. Our aim was to understand the effect of dopamine replacement therapy on various aspects of cognition. Whereas dorsal striatum receives dopamine input from the substantia nigra (SN), ventral striatum is innervated by dopamine-producing cells in the ventral tegmental area (VTA). In PD, degeneration of SN is substantially greater than cell loss in VTA and hence dopamine-deficiency is significantly greater in dorsal compared to ventral striatum. We suggest that dopamine supplementation improves functions mediated by dorsal striatum and impairs, or heightens to a pathological degree, operations ascribed to ventral striatum. We consider the extant literature in light of this principle. We also survey the effect of dopamine replacement on functional neuroimaging in PD relating the findings to this framework. This paper highlights the fact that currently, titration of therapy in PD is geared to optimizing dorsal striatum-mediated motor symptoms, at the expense of ventral striatum operations. Increased awareness of contrasting effects of dopamine replacement on dorsal versus ventral striatum functions will lead clinicians to survey a broader range of symptoms in determining optimal therapy, taking into account both those aspects of cognition that will be helped versus those that will be hindered by dopaminergic treatment.

scholarly journals A Guide to the Generation of a 6-Hydroxydopamine Mouse Model of Parkinson’s Disease for the Study of Non-Motor Symptoms

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 598
Author(s):  
Débora Masini ◽  
Carina Plewnia ◽  
Maëlle Bertho ◽  
Nicolas Scalbert ◽  
Vittorio Caggiano ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Survival Rates ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Motor Symptoms ◽  
Operative Care ◽  
6 Hydroxydopamine ◽  
Non Motor Symptoms

In Parkinson’s disease (PD), a large number of symptoms affecting the peripheral and central nervous system precede, develop in parallel to, the cardinal motor symptoms of the disease. The study of these conditions, which are often refractory to and may even be exacerbated by standard dopamine replacement therapies, relies on the availability of appropriate animal models. Previous work in rodents showed that injection of the neurotoxin 6-hydroxydopamine (6-OHDA) in discrete brain regions reproduces several non-motor comorbidities commonly associated with PD, including cognitive deficits, depression, anxiety, as well as disruption of olfactory discrimination and circadian rhythm. However, the use of 6-OHDA is frequently associated with significant post-surgical mortality. Here, we describe the generation of a mouse model of PD based on bilateral injection of 6-OHDA in the dorsal striatum. We show that the survival rates of males and females subjected to this lesion differ significantly, with a much higher mortality among males, and provide a protocol of enhanced pre- and post-operative care, which nearly eliminates animal loss. We also briefly discuss the utility of this model for the study of non-motor comorbidities of PD.

Cognitive Function in Parkinson's Disease: In Relation to Motor Symptoms

1989 ◽  
Vol 47 (3-4) ◽  
pp. 295-300 ◽  
Author(s):  
Yasuo Iwasaki ◽  
Masao Kinoshita ◽  
Ken Ikeda ◽  
Kiyoshi Takamiya
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Function ◽  
Motor Symptoms

Parkinsonism, Parkinson’s disease, and related conditions

2017 ◽  
pp. 897-906
Author(s):  
John V. Hindle ◽  
Sion Jones ◽  
Glesni Davies
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Older People ◽  
Lewy Bodies ◽  
Cell Loss ◽  
Brain Regions ◽  
Motor Symptoms ◽  
Advanced Care Planning ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is a progressive neurodegenerative condition characterized clinically by fatiguable bradykinesia, rigidity and tremor and pathologically by deposition of Lewy bodies and cell loss in the substantia nigra and other brain regions. Parkinsonism is the term used to describe the clinical features of conditions resembling PD. Their management requires specialist assessment and a multidisciplinary approach. Levodopa remains the mainstay of treatment for PD. Although other treatments are used, older people are more sensitive to their side effects. Non-motor symptoms, particularly neuropsychiatric problems, significantly impact quality of life and need special consideration in older people. Towards the later stage of the disease, management can be complex, and should involve advanced care planning.

scholarly journals Explorative Combined Lipid and Transcriptomic Profiling of Substantia Nigra and Putamen in Parkinson’s Disease

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1966 ◽  
Author(s):  
Helena Xicoy ◽  
Jos F. Brouwers ◽  
Bé Wieringa ◽  
Gerard J. M. Martens
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Molecular Mechanisms ◽  
Lipid Analysis ◽  
Dorsal Striatum ◽  
Receptor Subtype ◽  
Lipid Profiling ◽  
New Genes ◽  
Genes Encoding

Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons from the substantia nigra (SN) that project to the dorsal striatum (caudate-putamen). To better understand the molecular mechanisms underlying PD, we performed combined lipid profiling and RNA sequencing of SN and putamen samples from PD patients and age-matched controls. SN lipid analysis pointed to a neuroinflammatory component and included elevated levels of the endosomal lipid Bis (Monoacylglycero)Phosphate 42:8, while two of the three depleted putamen lipids were saturated sphingomyelin species. Remarkably, we observed gender-related differences in the SN and putamen lipid profiles. Transcriptome analysis revealed that the top-enriched pathways among the 354 differentially expressed genes (DEGs) in the SN were “protein folding” and “neurotransmitter transport”, and among the 261 DEGs from putamen “synapse organization”. Furthermore, we identified pathways, e.g., “glutamate signaling”, and genes, encoding, e.g., an angiotensin receptor subtype or a proprotein convertase, that have not been previously linked to PD. The identification of 33 genes that were common among the SN and putamen DEGs, which included the α-synuclein paralog β-synuclein, may contribute to the understanding of general PD mechanisms. Thus, our proof-of-concept data highlights new genes, pathways and lipids that have not been explored before in the context of PD.

scholarly journals Review of prodromal symptoms in Parkinson's Disease detected by MRI, EEG And microbiome

2019 ◽  
Author(s):  
Isabel Cristina Echeverri ◽  
Maria de la Iglesia Vayá ◽  
Jose Molina Mateo ◽  
Francia Restrepo de Mejia ◽  
Belarmino Segura Giraldo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Magnetic Resonance ◽  
Substantia Nigra ◽  
Evidence Synthesis ◽  
Magnetic Resonance Images ◽  
Event Related Potential ◽  
Motor Symptoms ◽  
The Brain ◽  
Early Parkinson’S Disease

Context: Parkinson’s disease (PD) is catalogued as a disorder that causes motor symptoms; the evidence of literature shows the PD starts with non-motor signs, which can be detected in prodromal phases. These previous phases can be analyzed and studied through magnetic resonance images (MRI), electroencephalography (EEG) and microbiome.Objective: To systematically review the areas of the brain and brain-gut axis which affect in early Parkinson’s disease that can possibly be visualized and analyzed by MRI, EEG and the microbiome.Evidence acquisition: Pubmed and Embase databases were used until July 30, 2018 as to search for early Parkinson’s disease at its earliest non-motor symptoms stage by using MRI, EEG, and microbiome. The search was performed according to the requirements of a systematic review. In order to identify reports, we evaluated them following the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. Evidence synthesis: MRI and EEG have provided the advances to find features for PD over the last decade. Those techniques identify motor symptoms on substantia nigra where the patient shows a dopamine deficiency. However, over recent years, researchers have found that PD has prodromal phases, that is, PD is not simply a neurodegenerative disorder characterized by the dysfunction of dopaminergic. Thus, high field MRI, event-related potential (ERP) and microbiota data shows a significant change on the brain cortex, white and grey matter, the extrapyramidal system, brain signals and the gut.Conclusion: The structural MRI is a useful technique in detecting the stages of motor symptoms on the substantia nigra in patients with PD. The use of magnetic resonance as an early detector requires a high magnetic field, as to identify the areas which diagnose that the patient could be in the premotor stages. On the other hand, EEG performed well in detecting PD features. Furthermore, microbiome sequencing might include the classification of bacterial families that could help to detect PD in its prodromal phase. Thus, the combination of all these techniques can support the possibility of diagnosing PD in its very early stages.

scholarly journals Association Between Decreased Srpk3 Expression And An Increase In Substantia Nigra Alpha-Synuclein Levels In An MPTP-Induced Parkinson’s Disease Mouse Model

2022 ◽  
Author(s):  
Min Hyung Seo ◽  
Sujung Yeo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Cell Loss ◽  
Alpha Synuclein ◽  
Mice Model ◽  
Dopaminergic Cell ◽  
The Brain

Abstract Parkinson’s disease (PD) is known as the second most common neurodegenerative disease, which is caused by destruction of dopaminergic neurons in the substantia nigra (SN) of the brain; however, the reason for the death of dopaminergic neurons remains unclear. An increase in α-synuclein (α-syn) is considered an important factor in the pathogenesis of PD. In the current study, we investigated the association between PD and serine/arginine-rich protein specific kinase 3 (Srpk3) in MPTP-induced parkinsonism mice model and in SH-SY5Y cells treated with MPP+. Srpk3 expression was significantly downregulated, while tyrosine hydroxylase (TH) decreased and α-synuclein (α-syn) increased after 4 weeks of MPTP intoxication treatment. Dopaminergic cell reduction and α-syn increase were demonstrated by inhibiting Srpk3 expression by siRNA in SH-SY5Y cells. Moreover, a decrease in Srpk3 expression upon siRNA treatment promoted dopaminergic cell reduction and α-syn increase in SH-SY5Y cells treated with MPP+. These results suggest that the decrease in Srpk3 expression due to Srpk3 siRNA caused both a decrease in TH and an increase in α-syn. This raises new possibilities for studying how Srpk3 controls dopaminergic cells and α-syn expression, which may be related to the pathogenesis of PD. Our results provide an avenue for understanding the role of Srpk3 during dopaminergic cell loss and α-syn increase in the SN. Furthermore, this study could support a therapeutic possibility for PD in that the maintenance of Srpk3 expression inhibited dopaminergic cell reduction.

scholarly journals Hyposmia as a marker of (non-)motor disease severity in Parkinson’s disease

2019 ◽  
Vol 126 (11) ◽  
pp. 1471-1478 ◽  
Author(s):  
Dareia S. Roos ◽  
Jos W. R. Twisk ◽  
Pieter G. H. M. Raijmakers ◽  
Richard L. Doty ◽  
Henk W. Berendse
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sleep Disturbances ◽  
Psychiatric Symptoms ◽  
Cell Loss ◽  
Motor Symptoms ◽  
Dopaminergic Cell ◽  
Dat Spect ◽  
Spect Scan ◽  
Non Motor Symptoms

Abstract The aim of this study was to evaluate the relationship of hyposmia in Parkinson’s disease (PD) with other motor and non-motor symptoms and with the degree of nigrostriatal dopaminergic cell loss. A total of 295 patients with a diagnosis of PD were included. Olfactory function was measured using the University of Pennsylvania Smell Identification Test (UPSIT). Motor symptoms were rated using the Unified Parkinson’s Disease Rating Scale motor subscale (UPDRS III). To evaluate other non-motor symptoms, we used the Mini-Mental State Examination (MMSE) as a measure of global cognitive function and validated questionnaires to assess sleep disturbances, psychiatric symptoms, and autonomic dysfunction. A linear regression model was used to calculate correlation coefficients between UPSIT score and motor and non-motor variables [for psychiatric symptoms a Poisson regression was performed]. In a subgroup of patients (n = 155) with a dopamine transporter (DaT) SPECT scan, a similar statistical analysis was performed, now including striatal DaT binding. In the regression models with correction for age, sex, disease duration, and multiple testing, all motor and non-motor symptoms were associated with UPSIT scores. In the subgroup of patients with a DaT-SPECT scan, there was a strong association between olfactory test scores and DaT binding in both putamen and caudate nucleus. Hyposmia in PD is associated with various motor and non-motor symptoms, like cognition, depression, anxiety, autonomic dysfunction and sleep disturbances, and with the degree of nigrostriatal dopaminergic cell loss. This finding adds further confirmation that hyposmia holds significant promise as a marker of disease progression.

scholarly journals Increased substantia nigra echogenicity correlated with visual hallucinations in Parkinson’s disease: a Chinese population-based study

2019 ◽  
Vol 41 (3) ◽  
pp. 661-667 ◽  
Author(s):  
Ting Li ◽  
Jing Shi ◽  
Bin Qin ◽  
Dongsheng Fan ◽  
Na Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Odds Ratio ◽  
Rating Scales ◽  
Binary Logistic Regression Analysis ◽  
Motor Symptoms ◽  
Visual Hallucinations ◽  
Roc Curve Analysis ◽  
Non Motor Symptoms

AbstractAs a noninvasive technique, transcranial sonography (TCS) of substantia nigra (SN) has gradually showed its effectiveness not only in diagnosis but also in understanding clinical features of Parkinson’s Disease (PD). This study aimed to further evaluate TCS for clinical diagnosis of PD, and to explore the association between sonographic manifestations and visual hallucinations (VH). A total of 226 subjects including 141 PD patients and 85 controls were recruited. All participants received TCS. A series of rating scales to evaluate motor and non-motor symptoms were performed in PD patients. Results showed that 172 subjects were successfully assessed by TCS. The area of SN was greater in PD patients than that in controls (P < 0.001). As receiver-operating characteristic (ROC) curve analysis showed, the best cutoff value for the larger SN echogenicity size was 23.5 mm2 (sensitivity 70.3%, specificity 77.0%). Patients with VH had larger SN area (P = 0.019), as well as higher Non-Motor Symptoms Scale (NMSS) scores (P = 0.018). Moreover, binary logistic regression analysis indicated that SN hyperechogenicity (odds ratio = 4.227, P = 0.012) and NMSS scores (odds ratio = 0.027, P = 0.042) could be the independent predictors for VH. In conclusion, TCS can be used as an auxiliary diagnostic tool for Parkinson’s disease. Increased SN echogenicity is correlated with VH in Parkinson’s disease, possibly because the brain stem is involved in the mechanism in the onset of VH. Further studies are needed to confirm these findings.

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