Reward Dependent Invigoration Relates to Theta Oscillations and Is Predicted by Dopaminergic Midbrain Integrity in Healthy Elderly

Steiger, Tineke K.; Bunzeck, Nico

doi:10.3389/fnagi.2017.00001

Cited by 86 publications

(126 citation statements)

References 75 publications

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“…A morphology similar to that which we observed in the SR 10 days after ischemia–an elongated rod-shaped nucleus and a body with short processes, is characteristic of rod-shaped microglia [ 55 , 56 , 57 , 58 ]. Rod-shaped microglia have been described in the cortex in rats with diffuse brain injury [ 56 ], in the hippocampus in older adults [ 58 ] and present in experimental models of optic nerve degeneration and in some slowly developing neurodegenerative diseases progressing to dementia [ 55 ].…”

Section: Discussionsupporting

confidence: 77%

Neurodegeneration, Myelin Loss and Glial Response in the Three-Vessel Global Ischemia Model in Rat

Ананьина

Kisel

Kudabaeva

et al. 2020

IJMS

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(1) Background: Although myelin disruption is an integral part of ischemic brain injury, it is rarely the subject of research, particularly in animal models. This study assessed for the first time, myelin and oligodendrocyte loss in a three-vessel model of global cerebral ischemia (GCI), which causes hippocampal damage. In addition, we investigated the relationships between demyelination and changes in microglia and astrocytes, as well as oligodendrogenesis in the hippocampus; (2) Methods: Adult male Wistar rats (n = 15) underwent complete interruption of cerebral blood flow for 7 min by ligation of the major arteries supplying the brain or sham-operation. At 10 and 30 days after the surgery, brain slices were stained for neurodegeneration with Fluoro-Jade C and immunohistochemically to assess myelin content (MBP+ percentage of total area), oligodendrocyte (CNP+ cells) and neuronal (NeuN+ cells) loss, neuroinflammation (Iba1+ cells), astrogliosis (GFAP+ cells) and oligodendrogenesis (NG2+ cells); (3) Results: 10 days after GCI significant myelin and oligodendrocyte loss was found only in the stratum oriens and stratum pyramidale. By the 30th day, demyelination in these hippocampal layers intensified and affected the substratum radiatum. In addition to myelin damage, activation and an increase in the number of microglia and astrocytes in the corresponding layers, a loss of the CA1 pyramidal neurons, and neurodegeneration in the neocortex and thalamus was observed. At a 10-day time point, we observed rod-shaped microglia in the substratum radiatum. Parallel with ongoing myelin loss on the 30th day after ischemia, we found significant oligodendrogenesis in demyelinated hippocampal layers; (4) Conclusions: Our study showed that GCI-simulating cardiac arrest in humans—causes not only the loss of pyramidal neurons in the CA1 field, but also the myelin loss of adjacent layers of the hippocampus.

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Section: Discussionsupporting

confidence: 77%

Neurodegeneration, Myelin Loss and Glial Response in the Three-Vessel Global Ischemia Model in Rat

Ананьина

Kisel

Kudabaeva

et al. 2020

IJMS

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“…This is exemplified by proteins such as S100B, which is released from astrocytes with neurotrophic or neurotoxic effects on neurons depending on their concentration and on the astrocytic activation state [ 71 , 72 ]. In turn, increased expression and secretion of S100B from astrocytes may be reflected in the CSF patterns as reported in traumatic brain injury [ 73 ], AD [ 74 , 75 ] and sCJD [ 76 ]. Consequently, astrocytes are turning into a potential target for therapeutic intervention in neurodegenerative diseases associated with an inflammatory component [ 77 ], indicating that astrocyte-associated metabolites may be potential biomarkers in biological fluids.…”

Section: Discussionmentioning

confidence: 99%

YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias

Llorens

Thüne

Tahir

et al. 2017

Mol Neurodegeneration

175

137

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BackgroundYKL-40 (also known as Chitinase 3-like 1) is a glycoprotein produced by inflammatory, cancer and stem cells. Its physiological role is not completely understood but YKL-40 is elevated in the brain and cerebrospinal fluid (CSF) in several neurological and neurodegenerative diseases associated with inflammatory processes. Yet the precise characterization of YKL-40 in dementia cases is missing.MethodsIn the present study, we comparatively analysed YKL-40 levels in the brain and CSF samples from neurodegenerative dementias of different aetiologies characterized by the presence of cortical pathology and disease-specific neuroinflammatory signatures.ResultsYKL-40 was normally expressed in fibrillar astrocytes in the white matter. Additionally YKL-40 was highly and widely expressed in reactive protoplasmic cortical and perivascular astrocytes, and fibrillar astrocytes in sporadic Creutzfeldt-Jakob disease (sCJD). Elevated YKL-40 levels were also detected in Alzheimer’s disease (AD) but not in dementia with Lewy bodies (DLB). In AD, YKL-40-positive astrocytes were commonly found in clusters, often around β-amyloid plaques, and surrounding vessels with β-amyloid angiopathy; they were also distributed randomly in the cerebral cortex and white matter. YKL-40 overexpression appeared as a pre-clinical event as demonstrated in experimental models of prion diseases and AD pathology.CSF YKL-40 levels were measured in a cohort of 288 individuals, including neurological controls (NC) and patients diagnosed with different types of dementia. Compared to NC, increased YKL-40 levels were detected in sCJD (p < 0.001, AUC = 0.92) and AD (p < 0.001, AUC = 0.77) but not in vascular dementia (VaD) (p > 0.05, AUC = 0.71) or in DLB/Parkinson’s disease dementia (PDD) (p > 0.05, AUC = 0.70). Further, two independent patient cohorts were used to validate the increased CSF YKL-40 levels in sCJD. Additionally, increased YKL-40 levels were found in genetic prion diseases associated with the PRNP-D178N (Fatal Familial Insomnia) and PRNP-E200K mutations.ConclusionsOur results unequivocally demonstrate that in neurodegenerative dementias, YKL-40 is a disease-specific marker of neuroinflammation showing its highest levels in prion diseases. Therefore, YKL-40 quantification might have a potential for application in the evaluation of therapeutic intervention in dementias with a neuroinflammatory component.Electronic supplementary materialThe online version of this article (10.1186/s13024-017-0226-4) contains supplementary material, which is available to authorized users.

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“…Meanwhile, NF-κB/p65 protein expression level was decreased as opposed to IκBa expression that was increased in BV-2 cells and primary microglia treated with LPS+LiCl. Moreover, the mRNA expression levels of pro-inflammatory cytokines IL-1β, IL-6, TNF-α and iNOS were decreased; on the other hand, the anti-inflammatory cytokine IL-10, a marker for M2 phenotype [ 26 ] was increased. It would appear therefore that IL-10 may be differentially regulated compared with the proinflammatory mediators and that LiCl promotes polarization of microglia from M1 to M2 [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the mRNA expression levels of pro-inflammatory cytokines IL-1β, IL-6, TNF-α and iNOS were decreased; on the other hand, the anti-inflammatory cytokine IL-10, a marker for M2 phenotype [ 26 ] was increased. It would appear therefore that IL-10 may be differentially regulated compared with the proinflammatory mediators and that LiCl promotes polarization of microglia from M1 to M2 [ 26 ]. The present results are consistent with Foltz et al [ 27 ] who reported that GSK-3β was able to phosphorylate Notch-1 in vitro , and that NICD has to be phosphorylated by GSK-3β for its translocation to the nucleus [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Production of proinflammatory mediators in activated microglia is synergistically regulated by Notch-1, glycogen synthase kinase (GSK-3β) and NF-κB/p65 signalling

et al. 2017

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Microglia activation and associated inflammatory response are involved in the pathogenesis of different neurodegenerative diseases. We have reported that Notch-1 and NF-κB/p65 signalling pathways operate in synergy in regulating the production of proinflammatory mediators in activated microglia. In the latter, there is also evidence by others that glycogen synthase kinase 3β (GSK-3β) mediates the release of proinflammatory cytokines but the interrelationships between the three signalling pathways have not been fully clarified. This is an important issue as activated microglia are potential therapeutic target for amelioration of microglia mediated neuroinflammation. Here we show that blocking of Notch-1 with N-[(3,5-Difluorophenyl) acetyl]-L-alanyl-2-phenylglycine-1,1-dimethylethyl ester (DAPT) in LPS activated BV-2 microglia not only suppressed Notch intracellular domain (NICD) and Hes-1 protein expression, but also that of GSK-3β. Conversely, blocking of the latter with lithium chloride (LiCl) decreased NICD expression in a dose-dependent manner; moreover, Hes-1 immunofluorescence was attenuated. Along with this, the protein expression level of p-GSK-3β and p-AKT protein expression was significantly increased. Furthermore, DAPT and LiCl decreased production of IL-1β, TNF-α, IL-6, iNOS, Cox2 and MCP-1; however, IL-10 expression was increased notably in LiCl treated cells. The effects of DAPT and LiCl on changes of the above-mentioned biomarkers were confirmed by immunofluorescence in both BV-2 and primary microglia. Additionally, NF-κB/p65 immunofluorescence was attenuated by DAPT and LiCl; as opposed to this, IκBα protein expression was increased. Taken together, it is suggested that Notch-1, NF-κB/p65 and GSK-3β operate in synergy to inhibit microglia activation. This may be effected via increased expression of phospho-GSK-3β (p-GSK-3β), phospho-protein kinase B (PKB) (p-AKT) and IκBα. It is concluded that the three signalling pathways are functionally interlinked in regulating microglia activation.

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Reward Dependent Invigoration Relates to Theta Oscillations and Is Predicted by Dopaminergic Midbrain Integrity in Healthy Elderly

Cited by 86 publications

References 75 publications

Neurodegeneration, Myelin Loss and Glial Response in the Three-Vessel Global Ischemia Model in Rat

Neurodegeneration, Myelin Loss and Glial Response in the Three-Vessel Global Ischemia Model in Rat

YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias

Production of proinflammatory mediators in activated microglia is synergistically regulated by Notch-1, glycogen synthase kinase (GSK-3β) and NF-κB/p65 signalling

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