scholarly journals Does Developmental Variability in the Number of Midbrain Dopamine Neurons Affect Individual Risk for Sporadic Parkinson’s Disease?

2020 ◽  
Vol 10 (2) ◽  
pp. 405-411 ◽  
Author(s):  
Christian U. von Linstow ◽  
Merritt DeLano-Taylor ◽  
Jeffrey H. Kordower ◽  
Patrik Brundin
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine Neurons ◽  
Individual Risk ◽  
Sporadic Parkinson’S Disease ◽  
Midbrain Dopamine ◽  
Midbrain Dopamine Neurons

scholarly journals Dopaminergic medication reduces striatal sensitivity to negative outcomes in Parkinson’s disease

2018 ◽  
Author(s):  
Brónagh McCoy ◽  
Sara Jahfari ◽  
Gwenda Engels ◽  
Tomas Knapen ◽  
Jan Theeuwes
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Learning Task ◽  
Dopamine Neurons ◽  
Negative Outcomes ◽  
Learning Differences ◽  
Dopaminergic Medication ◽  
Learning Rates ◽  
Approach Avoidance ◽  
Midbrain Dopamine

AbstractReduced levels of dopamine in Parkinson’s disease (PD) contribute to changes in learning, resulting from the loss of midbrain dopamine neurons that transmit a teaching signal to the striatum. Dopamine medication used by PD patients has previously been linked to either behavioral changes during learning itself or adjustments in approach and avoidance behavior after learning. To date, however, very little is known about the specific relationship between dopaminergic medication-driven differences during learning and subsequent changes in approach/avoidance tendencies in individual patients. We assessed 24 PD patients on and off dopaminergic medication and 24 healthy controls (HC) performing a probabilistic reinforcement learning task, while undergoing functional magnetic resonance imaging. During learning, medication in PD reduced an overemphasis on negative outcomes. When patients were on medication, learning rates were lower for negative (but not positive) outcomes and concurrent striatal BOLD responses showed reduced prediction error sensitivity. Medication-induced shifts in negative learning rates were predictive of changes in approach/avoidance choice patterns after learning, and these changes were accompanied by striatal BOLD response alterations. These findings highlight dopamine-driven learning differences in PD and provide new insight into how changes in learning impact the transfer of learned value to approach/avoidance responses in novel contexts.

scholarly journals Spatial RNA Sequencing Identifies Robust Markers of Vulnerable and Resistant Human Midbrain Dopamine Neurons and Their Expression in Parkinson’s Disease

2021 ◽  
Vol 14 ◽  
Author(s):  
Julio Aguila ◽  
Shangli Cheng ◽  
Nigel Kee ◽  
Ming Cao ◽  
Menghan Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Small Sample ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Minimal Sample ◽  
Differential Vulnerability ◽  
Minimal Sample Size ◽  
Midbrain Dopamine ◽  
Small Sample Sizes

Defining transcriptional profiles of substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) dopamine neurons is critical to understanding their differential vulnerability in Parkinson’s Disease (PD). Here, we determine transcriptomes of human SNc and VTA dopamine neurons using LCM-seq on a large sample cohort. We apply a bootstrapping strategy as sample input to DESeq2 and identify 33 stably differentially expressed genes (DEGs) between these two subpopulations. We also compute a minimal sample size for identification of stable DEGs, which highlights why previous reported profiles from small sample sizes display extensive variability. Network analysis reveal gene interactions unique to each subpopulation and highlight differences in regulation of mitochondrial stability, apoptosis, neuronal survival, cytoskeleton regulation, extracellular matrix modulation as well as synapse integrity, which could explain the relative resilience of VTA dopamine neurons. Analysis of PD tissues showed that while identified stable DEGs can distinguish the subpopulations also in disease, the SNc markers SLIT1 and ATP2A3 were down-regulated and thus appears to be biomarkers of disease. In summary, our study identifies human SNc and VTA marker profiles, which will be instrumental for studies aiming to modulate dopamine neuron resilience and to validate cell identity of stem cell-derived dopamine neurons.

scholarly journals Disease Duration Influences Gene Expression in Neuromelanin-Positive Cells From Parkinson’s Disease Patients

2021 ◽  
Vol 14 ◽  
Author(s):  
Katarína Tiklová ◽  
Linda Gillberg ◽  
Nikolaos Volakakis ◽  
Hilda Lundén-Miguel ◽  
Lina Dahl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Lewy Body Disease ◽  
Dopamine Neurons ◽  
Differentially Expressed ◽  
Incidental Lewy Body Disease ◽  
Advanced Stages ◽  
Midbrain Dopamine

Analyses of gene expression in cells affected by neurodegenerative disease can provide important insights into disease mechanisms and relevant stress response pathways. Major symptoms in Parkinson’s disease (PD) are caused by the degeneration of midbrain dopamine (mDA) neurons within the substantia nigra. Here we isolated neuromelanin-positive dopamine neurons by laser capture microdissection from post-mortem human substantia nigra samples recovered at both early and advanced stages of PD. Neuromelanin-positive cells were also isolated from individuals with incidental Lewy body disease (ILBD) and from aged-matched controls. Isolated mDA neurons were subjected to genome-wide gene expression analysis by mRNA sequencing. The analysis identified hundreds of dysregulated genes in PD. Results showed that mostly non-overlapping genes were differentially expressed in ILBD, subjects who were early after diagnosis (less than five years) and those autopsied at more advanced stages of disease (over five years since diagnosis). The identity of differentially expressed genes suggested that more resilient, stably surviving DA neurons were enriched in samples from advanced stages of disease, either as a consequence of positive selection of a less vulnerable long-term surviving mDA neuron subtype or due to up-regulation of neuroprotective gene products.

scholarly journals Disease‐specific phenotypes in dopamine neurons from human iPS‐based models of genetic and sporadic Parkinson's disease

2012 ◽  
Vol 4 (5) ◽  
pp. 380-395 ◽  
Author(s):  
Adriana Sánchez‐Danés ◽  
Yvonne Richaud‐Patin ◽  
Iria Carballo‐Carbajal ◽  
Senda Jiménez‐Delgado ◽  
Carles Caig ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine Neurons ◽  
Sporadic Parkinson’S Disease ◽  
Disease Specific
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