Astrocytes in Parkinson's disease: from preclinical assays to in vivo imaging and therapeutic probes

Zeng, Zhou; Roussakis, Andreas–Antonios; Lao–Kaim, Nicholas P; Piccini, Paola

doi:10.1016/j.neurobiolaging.2020.07.012

Cited by 10 publications

(13 citation statements)

References 102 publications

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“…8 Nevertheless, the findings from PD postmortem studies on GFAP expression are inconsistent, since some have revealed GFAP upregulation and typical reactive morphology and others, minimal or mild astrogliosis in patients with PD. 5 The finding of decreased GFAP expression in active participants corroborated with studies in PD-like rat models that have described reduced GFAP, dopaminergic neuron protection, and improvements in motor behavior after a treadmill exercise protocol. 16 In human postmortem material, there is a decrease in axonal transport in subjects in early phases of PD when compared to subjects without dopaminergic degeneration.…”

Section: Discussionsupporting

confidence: 62%

“…After taking up α-synuclein, astrocytes are proposed to release cytokines including tumor necrosis factor and interleukin-6, thereby causing inflammatory responses, which can promote PD progression. 5 However, the exact role of these cells on the pathophysiology of PD is still controversial, since they can also be active anti-inflammatory pathways. 8 Nevertheless, the findings from PD postmortem studies on GFAP expression are inconsistent, since some have revealed GFAP upregulation and typical reactive morphology and others, minimal or mild astrogliosis in patients with PD.…”

Section: Discussionmentioning

confidence: 99%

“…Astrocytes, the most present class of glial cells in the mammalian central nervous system (CNS), has been highlighted as key molecule of neuroinflammation and has a very heterogeneous functional level. 5 Glial fibrillary acidic protein (GFAP) is a protein expressed in astrocytes widely described for having a relationship with neurodegenerative disease progression and CNS injuries, 6 as well as dysregulation of nervous system homeostasis. 7 Recently, research on neurodegenerative disorders has focused on understanding the role of astrogliosis in the disease pathophysiology, and has also been seem as a promising cellular source not only to study CNS pathologies initiation and progression, but also as a therapeutic target.…”

Section: Introductionmentioning

confidence: 99%

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Active lifestyle enhances protein expression profile in subjects with Lewy body pathology

Real

Suemoto

Binda

et al. 2021

Dement. neuropsychol.

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ABSTRACT. Clinical trials of the effects of physical activity have reported improvements in symptoms and quality of life in patients with Parkinson's disease (PD). Additionally, morphological brain changes after exercising were reported in PD animal models. However, these lifestyle-related changes were not evaluated in postmortem brain tissue. Objective: We aimed to evaluate, by immunohistochemistry, astrocytes, tyrosine hydroxylase (TH) and structural proteins expression (neurofilaments and microtubules — MAP2) changes in postmortem brain samples of individuals with Lewy body pathology. Methods: Braak PD stage≥III samples, classified by neuropathology analysis, from The Biobank for Aging Studies were classified into active (n=12) and non-active (n=12) groups, according to physical activity lifestyle, and paired by age, sex and Braak staging. Substantia nigra and basal ganglia were evaluated. Results: Groups were not different in terms of age or gender and had similar PD neuropathological burden (p=1.00). We observed higher TH expression in the active group in the substantia nigra and the basal ganglia (p=0.04). Astrocytes was greater in the non-active subjects in the midbrain (p=0.03) and basal ganglia (p=0.0004). MAP2 levels were higher for non-active participants in the basal ganglia (p=0.003) and similar between groups in the substantia nigra (p=0.46). Neurofilament levels for non-active participants were higher in the substantia nigra (p=0.006) but not in the basal ganglia (p=0.24). Conclusion: Active lifestyle seems to promote positive effects on brain by maintaining dopamine synthesis and structural protein expression in the nigrostriatal system and decrease astrogliosis in subjects with the same PD neuropathology burden.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Active lifestyle enhances protein expression profile in subjects with Lewy body pathology

Real

Suemoto

Binda

et al. 2021

Dement. neuropsychol.

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“…The number of GFAP-positive astrocytes and their activation state were increased in the ventral CN and primary AC, but not in the MGB. Astrocytes are important in regulating levels of neurotransmitter and ion concentrations, controlling synapse formation and function, and repairing the nervous system [52,53]. In response to neuronal degeneration, they promote synaptic regrowth and axonal sprouting [22,54].…”

Section: Neuroglial Involvement In Tinnitusmentioning

confidence: 99%

The Role of Inflammation in Tinnitus: A Systematic Review and Meta-Analysis

Mennink

Aalbers

Dijk

et al. 2022

JCM

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Subjective tinnitus is the perception of sound without the presence of an external source. Increasing evidence suggests that tinnitus is associated with inflammation. In this systematic review, the role of inflammation in subjective tinnitus was studied. Nine animal and twenty human studies reporting inflammatory markers in both humans and animals with tinnitus were included. It was established that TNF-α and IL-1β are increased in tinnitus, and that microglia and astrocytes are activated as well. Moreover, platelet activation may also play a role in tinnitus. In addition, we elaborate on mechanisms of inflammation in tinnitus, and discuss potential treatment options targeting inflammatory pathways.

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“…Yet, we found that LPS plus paraquat also induced increase in astroglia marker (at least a subset of astrocytes, as determined by GFAP) and this was unaffected by the DSS treatments. These cells could be of importance to the present outcomes given that there is a large literature suggesting a role for astrogliosis in PD [73]. In any case, it was interesting that microglia appear more influenced or tied to the DSS-induced gut changes than were astrocytes.…”

Section: Discussionmentioning

confidence: 86%

The impact of dextran sodium sulphate and probiotic pre-treatment in a murine model of Parkinson’s disease

Dwyer

Chaiquin

Ayoub

et al. 2021

J Neuroinflammation

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Background Recent work has established that Parkinson’s disease (PD) patients have an altered gut microbiome, along with signs of intestinal inflammation. This could help explain the high degree of gastric disturbances in PD patients, as well as potentially be linked to the migration of peripheral inflammatory factors into the brain. To our knowledge, this is the first study to examine microbiome alteration prior to the induction of a PD murine model. Methods We presently assessed whether pre-treatment with the probiotic, VSL #3, or the inflammatory inducer, dextran sodium sulphate (DSS), would influence the PD-like pathology provoked by a dual hit toxin model using lipopolysaccharide (LPS) and paraquat exposure. Results While VSL #3 has been reported to have anti-inflammatory effects, DSS is often used as a model of colitis because of the gut inflammation and the breach of the intestinal barrier that it induces. We found that VSL#3 did not have any significant effects (beyond a blunting of LPS paraquat-induced weight loss). However, the DSS treatment caused marked changes in the gut microbiome and was also associated with augmented behavioral and inflammatory outcomes. In fact, DSS markedly increased taxa belonging to the Bacteroidaceae and Porphyromonadaceae families but reduced those from Rikencellaceae and S24-7, as well as provoking colonic pro-inflammatory cytokine expression, consistent with an inflamed gut. The DSS also increased the impact of LPS plus paraquat upon microglial morphology, along with circulating lipocalin-2 (neutrophil marker) and IL-6. Yet, neither DSS nor VSL#3 influenced the loss of substantia nigra dopamine neurons or the astrocytic and cytoskeleton remodeling protein changes that were provoked by the LPS followed by paraquat treatment. Conclusions These data suggest that disruption of the intestinal integrity and the associated microbiome can interact with systemic inflammatory events to promote widespread brain-gut changes that could be relevant for PD and at the very least, suggestive of novel neuro-immune communication.

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Astrocytes in Parkinson's disease: from preclinical assays to in vivo imaging and therapeutic probes

Cited by 10 publications

References 102 publications

Active lifestyle enhances protein expression profile in subjects with Lewy body pathology

Active lifestyle enhances protein expression profile in subjects with Lewy body pathology

The Role of Inflammation in Tinnitus: A Systematic Review and Meta-Analysis

The impact of dextran sodium sulphate and probiotic pre-treatment in a murine model of Parkinson’s disease

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