scholarly journals 5-HT2AReceptor Binding in the Frontal Cortex of Parkinson’s Disease Patients and Alpha-Synuclein Overexpressing Mice: A Postmortem Study

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Nadja Bredo Rasmussen ◽  
Mikkel Vestergaard Olesen ◽  
Tomasz Brudek ◽  
Per Plenge ◽  
Anders Bue Klein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Executive Function ◽  
Transgenic Mice ◽  
Frontal Cortex ◽  
Receptor Binding ◽  
Alpha Synuclein ◽  
Association Cortex ◽  
Motor Disorder

The5-HT2Areceptor is highly involved in aspects of cognition and executive function and seen to be affected in neurodegenerative diseases like Alzheimer’s disease and related to the disease pathology. Even though Parkinson’s disease (PD) is primarily a motor disorder, reports of impaired executive function are also steadily being associated with this disease. Not much is known about the pathophysiology behind this. The aim of this study was thereby twofold: (1) to investigate5-HT2Areceptor binding levels in Parkinson’s brains and (2) to investigate whether PD associated pathology, alpha-synuclein (AS) overexpression, could be associated with5-HT2Aalterations. Binding density for the5-HT2A-specific radioligand [3H]-MDL 100.907 was measured in membrane suspensions of frontal cortex tissue from PD patients. Protein levels of AS were further measured using western blotting. Results showed higher AS levels accompanied by increased5-HT2Areceptor binding in PD brains. In a separate study, we looked for changes in5-HT2Areceptors in the prefrontal cortex in 52-week-old transgenic mice overexpressing human AS. We performed region-specific5-HT2Areceptor binding measurements followed by gene expression analysis. The transgenic mice showed lower5-HT2Abinding in the frontal association cortex that was not accompanied by changes in gene expression levels. This study is one of the first to look at differences in serotonin receptor levels in PD and in relation to AS overexpression.

The Effect of Dopamine on Gene Expression of Alpha-synuclein and Transcription Factors GATA-1, GATA-2, and ZSCAN21 in Parkinson’s Disease

2018 ◽  
Vol 12 (5) ◽  
pp. 410-418
Author(s):  
A. K. Emelyanov ◽  
A. O. Lavrinova ◽  
E. M. Litusova ◽  
N. A. Knyazev ◽  
D. G. Kulabukhova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Alpha Synuclein

Gene expression of the nicotinic acetylcholine receptor α4 subunit in the frontal cortex in Parkinson's disease patients

1995 ◽  
Vol 187 (3) ◽  
pp. 173-176 ◽  
Author(s):  
Hannsjörg Schröder ◽  
Robert A.I. de Vos ◽  
Ernst N.H. Jansen ◽  
Christina Birtsch ◽  
Andrea Wevers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Frontal Cortex ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine

scholarly journals Alpha-Synuclein transgenic mice, h-α-SynL62, display α-Syn aggregation and a dopaminergic phenotype reminiscent of Parkinson’s disease

2018 ◽  
Vol 339 ◽  
pp. 153-168 ◽  
Author(s):  
Silke Frahm ◽  
Valeria Melis ◽  
David Horsley ◽  
Janet E. Rickard ◽  
Gernot Riedel ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transgenic Mice ◽  
Alpha Synuclein

scholarly journals Transgenic mice expressing human alpha-synuclein in noradrenergic neurons develop locus coeruleus pathology and non-motor features of Parkinson’s disease

2019 ◽  
Author(s):  
LM Butkovich ◽  
MC Houser ◽  
T Chalermpalanupap ◽  
KA Porter-Stransky ◽  
AF Iannitelli ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transgenic Mice ◽  
Locus Coeruleus ◽  
Transgenic Mouse ◽  
Alpha Synuclein ◽  
Striatal Dopamine ◽  
Motor Symptoms ◽  
Age Dependent ◽  
Non Motor Symptoms

AbstractDegeneration of locus coeruleus (LC) neurons and dysregulation of noradrenergic signaling are ubiquitous features of Parkinson’s disease (PD). The LC is among the first brain regions affected by α-synuclein (asyn) pathology, yet how asyn affects these neurons remains unclear. LC-derived norepinephrine (NE) can stimulate neuroprotective mechanisms and modulate immune cells, while dysregulation of NE neurotransmission may exacerbate disease progression, particularly non-motor symptoms, and contribute to the chronic neuroinflammation associated with PD pathology. Although transgenic mice overexpressing asyn have previously been developed, transgene expression is usually driven by pan-neuronal promoters and thus has not been selectively targeted to LC neurons. Here we report a novel transgenic mouse expressing human wild-type asyn under control of the noradrenergic-specific dopamine β-hydroxylase promoter. These mice developed oligomeric and conformation-specific asyn in LC neurons, alterations in hippocampal and LC microglial abundance, upregulated GFAP expression, degeneration of LC fibers, decreased striatal dopamine (DA) metabolism, and age-dependent behaviors reminiscent of non-motor symptoms of PD that were rescued by adrenergic receptor antagonists. These mice provide novel insights into how asyn pathology affects LC neurons and how central noradrenergic dysfunction may contribute to early PD pathophysiology.Significance statementα-synuclein (asyn) pathology and loss of neurons in the locus coeruleus (LC) are two of the most ubiquitous neuropathologic features of Parkinson’s disease (PD). Dysregulated NE neurotransmission is associated with the non-motor symptoms of PD including sleep disturbances, emotional changes such as anxiety and depression, and cognitive decline. Importantly, loss of central NE may contribute to the chronic inflammation in, and progression of, PD. We have generated a novel transgenic mouse expressing human asyn in LC neurons to investigate how increased asyn expression affects the function of the central noradrenergic transmission and associated behaviors. We report cytotoxic effects of oligomeric and conformation-specific asyn, astrogliosis, LC fiber degeneration, disruptions in striatal dopamine metabolism, and age-dependent alterations in non-motor behaviors without inclusions.

scholarly journals Synapsin III gene silencing redeems alpha-synuclein transgenic mice from Parkinson’s disease-like phenotype

2022 ◽  
Author(s):  
Gaia Faustini ◽  
Francesca Longhena ◽  
Anna Masato ◽  
Valentina Bassareo ◽  
Roberto Frau ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transgenic Mice ◽  
Gene Silencing ◽  
Alpha Synuclein ◽  
Synapsin Iii

scholarly journals Neurodegeneration and neuroinflammation are linked, but independent of α-synuclein inclusions, in a seeding/spreading mouse model of Parkinson’s disease

2020 ◽  
Author(s):  
Pierre Garcia ◽  
Wiebke Jürgens-Wemheuer ◽  
Oihane Uriarte ◽  
Kristopher J Schmit ◽  
Annette Masuch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Active Role ◽  
Brain Regions ◽  
Alpha Synuclein ◽  
Intracerebral Injection ◽  
Inclusion Formation

AbstractA key process of neurodegeneration in Parkinson’s disease (PD) is the transneuronal spreading of α-synuclein. Alpha-synuclein is a presynaptic protein that is implicated in the pathogenesis of PD and other synucleinopathies, where it forms, upon intracellular aggregation, pathological inclusions. Other hallmarks of PD include neurodegeneration and microgliosis in susceptible brain regions. Whether it is primarily transneuronal spreading of α-synuclein particles, inclusion formation, or other mechanisms, such as inflammation, that cause neurodegeneration in PD is unclear. We used spreading/aggregation of α-synuclein induced by intracerebral injection of α-synuclein preformed fibrils into the mouse brain to address this question. We performed quantitative histological analysis for α-synuclein inclusions, neurodegeneration, and microgliosis in different brain regions, and a gene expression profiling of the ventral midbrain, at two different timepoints after disease induction. We observed significant neurodegeneration and microgliosis in brain regions not only with, but also without α-synuclein inclusions. We also observed prominent microgliosis in injured brain regions that did not correlate with neurodegeneration nor with inclusion load. In longitudinal gene expression profiling experiments, we observed early and unique alterations linked to microglial mediated inflammation that preceded neurodegeneration, indicating an active role of microglia in inducing neurodegeneration. Our observations indicate that α-synuclein inclusion formation is not the major driver in the early phases of PD-like neurodegeneration, but that diffusible, oligomeric α-synuclein species, which induce unusual microglial reactivity, play a key role in this process. Our findings uncover new features of α-synuclein induced pathologies, in particular microgliosis, and point to the necessity of a broader view of the process of “prion-like spreading” of that protein.

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