Cytokine profiling in the prefrontal cortex of Parkinson's Disease and Multiple System Atrophy patients

Rydbirk, Rasmus; Elfving, Betina; Andersen, Mille Dahl; Langbøl, Mia; Folke, Jonas; Winge, Kristian; Pakkenberg, Bente; Brudek, Tomasz; Aznar, Susana

doi:10.1016/j.nbd.2017.07.014

Cited by 54 publications

(73 citation statements)

References 59 publications

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“…Of interest, both MSA [65][66][67] and HDLS [68] share pathological astro-and microgliosis. In a previous study we found that MSA patients had lower protein levels of G-CSF, a growth factor belonging to the same family as CSF, in the prefrontal cortex of MSA brains [20]. These observations seem to support each other, as the observed decline in non-classical monocytes observed in blood of MSA patients is probably associated with the neuroinflammatory state of the patients.…”

Section: Discussionsupporting

confidence: 60%

“…The aim of the study was to identify gene-specific epigenetic changes as well as the affected biological functions. From previous studies, we know that the prefrontal cortex is affected in MSA [20]. We validated the results from the BeadChip using NGS-based amplicon sequencing and performed RT-qPCR to confirm gene expression alterations of immune related components.…”

Section: Introductionmentioning

confidence: 83%

“…Table 3, Online Resource 1. RNA was extracted using the miRNeasy Mini Kit (Qiagen; #217004) following the manufacturer's instructions [20]. The protocol is described in detail in Online Resource 2.…”

Section: Rna Expression Analysismentioning

confidence: 99%

“…The protocol is described in detail in Online Resource 2. Reverse transcription quantitative real-time PCR was performed as earlier described [20] in accordance with the MIQE guidelines [46]. We utilized primers for AREL1 (PrimerBank ID [47]: 87116667c3, 132 bps) and MHC Class I HLAs (covering HLAs A-C and E-G; F: 5-CCTACGACGGCAAGGATT AC-3, R: 5-TGCCAGGTCAGTGTGATCTC-3 [48], 304 bps).…”

Section: Rna Expression Analysismentioning

confidence: 99%

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Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients

Rydbirk

Folke

Busato

et al. 2020

acta neuropathol commun

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Multiple system atrophy (MSA) is a rare disease with a fatal outcome. To date, little is known about the molecular processes underlying disease development. Its clinical overlap with related neurodegenerative movement disorders underlines the importance for expanding the knowledge of pathological brain processes in MSA patients to improve distinction from similar diseases. In the current study, we investigated DNA methylation changes in brain samples from 41 MSA patients and 37 healthy controls. We focused on the prefrontal cortex, a moderately affected area in MSA. Using Illumina MethylationEPIC arrays, we investigated 5-methylcytosine (5mC) as well as 5-hydroxymethylcytosine (5hmC) changes throughout the genome. We identified five significantly different 5mC probes (adj. P < 0.05), of which one probe mapping to the AREL1 gene involved in antigen presentation was decreased in MSA patients. This decrease correlated with increased 5hmC levels. Further, we identified functional DNA methylation modules involved in inflammatory processes. As expected, the decreased 5mC levels on AREL1 was concordant with increased gene expression levels of both AREL1 as well as MHC Class I HLA genes in MSA brains. We also investigated whether these changes in antigen-related processes in the brain associated with changes in peripheral mononuclear cells. Using flow cytometry on an independent cohort of MSA patients, we identified a decrease in circulating non-classical CD14 + CD16 ++ blood monocytes, whereas T and NK cell populations were unchanged. Taken together, our results support the view of an active neuroimmune response in brains of MSA patients.

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Section: Discussionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 83%

Section: Rna Expression Analysismentioning

confidence: 99%

Section: Rna Expression Analysismentioning

confidence: 99%

See 2 more Smart Citations

Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients

Rydbirk

Folke

Busato

et al. 2020

acta neuropathol commun

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“…In the pathogenic mechanisms of PD, a crucial role has been indicated for activated pro-inflammatory astrocytes, also involving the overproduction and release of S100B, in response to striatal dopaminergic denervation or 6-hydroxydopamine administration Morales et al 2016). S100B was over-expressed in crucial brain regions such as substantia nigra and striatum both in PD patients (Sathe et al 2012;Rydbirk et al 2017) and in MPTP-treated mice (Sathe et al 2012;Viana et al 2016). In addition, transgenic mice over-expressing S100B have been reported to develop features of PD, such as the impairment of motor coordination and the expression of some molecular parameters, including the dopamine-D2 receptor (Liu et al 2011).…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

The S100B story: from biomarker to active factor in neural injury

Michetti

D’Ambrosi

Toesca

et al. 2018

Journal of Neurochemistry

289

238

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S100B is a Ca -binding protein mainly concentrated in astrocytes. Its levels in biological fluids (cerebrospinal fluid, peripheral and cord blood, urine, saliva, amniotic fluid) are recognized as a reliable biomarker of active neural distress. Although the wide spectrum of diseases in which the protein is involved (acute brain injury, neurodegenerative diseases, congenital/perinatal disorders, psychiatric disorders) reduces its specificity, its levels remain an important aid in monitoring the trend of the disorder. Mounting evidence now points to S100B as a Damage-Associated Molecular Pattern molecule which, when released at high concentration, through its Receptor for Advanced Glycation Endproducts, triggers tissue reaction to damage in a series of different neural disorders. This review addresses this novel scenario, presenting data indicating that S100B levels and/or distribution in the nervous tissue of patients and/or experimental models of different neural disorders, for which the protein is used as a biomarker, are directly related to the progress of the disease: acute brain injury (ischemic/hemorrhagic stroke, traumatic injury), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis), congenital/perinatal disorders (Down syndrome, spinocerebellar ataxia-1), psychiatric disorders (schizophrenia, mood disorders), inflammatory bowel disease. In many cases, over-expression/administration of the protein induces worsening of the disease, whereas its deletion/inactivation produces amelioration. This review points out that the pivotal role of the protein resulting from these data, opens the perspective that S100B may be regarded as a therapeutic target for these different diseases, which appear to share some common features reasonably attributable to neuroinflammation, regardless their origin.

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De novo tetrahydrobiopterin biosynthesis is impaired in the inflammed striatum of parkin^(−/−) mice

Martins

Glaser

Aguiar

et al. 2018

Cell Biology International

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Parkinson's disease (PD), the second-most prevalent neurodegenerative disease, is primarily characterized by neurodegeneration in the substantia nigra pars compacta, resulting in motor impairment. Loss-of-function mutations in parkin are the major cause of the early onset familial form of the disease. Although rodents deficient in parkin (parkin ) have some dopaminergic system dysfunction associated with central oxidative stress and energy metabolism deficiencies, these animals only display nigrostriatal pathway degeneration under inflammatory conditions. This study investigated the impact of the inflammatory stimulus induced by lypopolisaccharide (LPS) on tetrahydrobiopterin (BH4) synthesizing enzymes (de novo and salvage pathways), since this cofactor is essential for dopamine synthesis. The mitochondrial content and architecture was investigated in the striatum of LPS-exposed parkin mice. As expected, the LPS (0.33 mg/kg; i.p.) challenge compromised spontaneous locomotion and social interaction with juvenile parkin and WT mice. Moreover, the genotype impacted the kinetics of the investigation of the juvenile. The inflammatory scenario did not induce apparent changes in mitochondrial ultrastructure; however, it increased the quantity of mitochondria, which were of smaller size, and provoked the perinuclear distribution of the organelle. Furthermore, the BH4 de novo biosynthetic pathway failed to be up-regulated in the LPS challenge, a well-known stimulus for its activation. The LPS treatment increased sepiapterin reductase (SPR) expression, suggesting compensation by the salvage pathway. This might indicate that dopamine synthesis is compromised in parkin mice under inflammatory conditions. Finally, this scenario impaired the striatal expression of the transcription factor BDNF, possibly favoring cell death.

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Cytokine profiling in the prefrontal cortex of Parkinson's Disease and Multiple System Atrophy patients

Cited by 54 publications

References 59 publications

Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients

Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients

The S100B story: from biomarker to active factor in neural injury

De novo tetrahydrobiopterin biosynthesis is impaired in the inflammed striatum of parkin^(−/−) mice

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Cytokine profiling in the prefrontal cortex of Parkinson's Disease and Multiple System Atrophy patients

Cited by 54 publications

References 59 publications

Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients

Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients

The S100B story: from biomarker to active factor in neural injury

De novo tetrahydrobiopterin biosynthesis is impaired in the inflammed striatum of parkin(−/−) mice

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De novo tetrahydrobiopterin biosynthesis is impaired in the inflammed striatum of parkin^(−/−) mice