Fluorocitrate induced the alterations of memory-related proteins and tau hyperphosphorylation in SD rats

Xiao-ling, Shang; Wang, Quanbao; Liu, Xiuping; Yao, Xiu-Qing; Cao, Fuliang; Wang, Qun; Zhang, Jia Yu; Wang, Jian‐Zhi; Liu, Gongping

doi:10.1016/j.neulet.2014.10.036

Cited by 13 publications

(4 citation statements)

References 33 publications

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“…Energy hypometabolism is found in AD patients, and evidence suggests this is important at the beginning of AD [ 78 ]. Although the effects of FC on AD are not entirely understood, in an animal model of AD induced by Aβ1-42 injection in the hippocampus, FC was found to reduce the acquisition of spatial memory [ 79 ] and also increased tau phosphorylation in the hippocampus [ 80 ]. Regarding Aβ-metabolism and its accumulation, similarly to MG, FC did not cause any alteration in our conditions.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Astroglial Dysfunction Induced by Neurotoxins: Mimicking Astrocytic Metabolic Alterations of Alzheimer’s Disease

Taday,

Fróes,

Seady

et al. 2024

Metabolites

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Astrocytes play fundamental roles in the maintenance of brain homeostasis. The dysfunction of these cells is widely associated with brain disorders, which are often characterized by variations in the astrocyte protein markers GFAP and S100B, in addition to alterations in some of its metabolic functions. To understand the role of astrocytes in neurodegeneration mechanisms, we induced some of these metabolic alterations, such as energy metabolism, using methylglyoxal (MG) or fluorocitrate (FC); and neuroinflammation, using lipopolysaccharide (LPS) and streptozotocin (STZ), which is used for inducing Alzheimer’s disease (AD) in animal models. We showed that MG, LPS, STZ and FC similarly caused astrocyte dysfunction by increasing GFAP and reducing S100B secretion. In the context of AD, STZ caused an amyloid metabolism impairment verified by increases in Aβ1-40 peptide content and decreases in the amyloid degradation enzymes, IDE and NEP. Our data contribute to the understanding of the role of astrocytes in brain injury mechanisms and suggest that STZ is suitable for use in vitro models for studying the role of astrocytes in AD.

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Section: Discussionmentioning

confidence: 99%

In Vitro Astroglial Dysfunction Induced by Neurotoxins: Mimicking Astrocytic Metabolic Alterations of Alzheimer’s Disease

Taday,

Fróes,

Seady

et al. 2024

Metabolites

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“…FC have been classically used for astrocytic inactivation, resulting in pathophysiological studies of Alzheimer’s disease, neuroinflammation, ischemia, depression and traumatic brain injury, in order to both understand cellular mechanisms and promote therapeutic strategies [ 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. This compound targets the aconitase enzyme, binding strongly to it and then interrupting the Krebs cycle.…”

Section: Discussionmentioning

confidence: 99%

S100B Secretion in Astrocytes, Unlike C6 Glioma Cells, Is Downregulated by Lactate

Selistre,

Rodrigues,

Federhen

et al. 2023

Metabolites

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S100B is a calcium-binding protein produced and secreted by astrocytes in response to various extracellular stimuli. C6 glioma cells are a lineage commonly employed for astroglial studies due to the expression of astrocyte specific markers and behavior. However, in high-glucose medium, C6 S100B secretion increases, in contrast to the trend in primary astrocyte cultures. Additionally, S100B secretion decreases due to fluorocitrate (FC), a Krebs cycle inhibitor, highlighting a connection between S100B and metabolism. Herein, we investigate the impact of FC on S100B secretion in primary astrocyte cultures, acute hippocampal slices and C6 glioma cells, as well as lactate mediation. Our results demonstrated that C6 responded similarly to astrocytes in various parameters, despite the decrease in S100B secretion, which was inversely observed in astrocytes and slices. Furthermore, FC inversely altered extracellular lactate in both models, suggesting a role for lactate in S100B secretion. This was reinforced by a decrease in S100B secretion in hippocampal slices treated with lactate and its agonist, but not in C6 cells, despite HCAR1 expression. Our findings indicate that extracellular lactate mediates the decrease in S100B secretion in astrocytes exposed to FC. They also emphasize the differences in C6 glioma cells regarding energetic metabolism. The proposed mechanism via HCAR1 provides further compelling evidence of the relationship between S100B and glucose metabolism.

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“…Both FC and GI may have the therapeutic applications in diminishing the in ammatory response of glia cells. FC, preferentially taken up by astrocytes is the reversible inhibitor of the tricarboxylic acid cycle [45].…”

Section: Discussionmentioning

confidence: 99%

A1 Reactive Astrocytes Activated by 2-chloroethanol Modulate M1 Microglia Polarization through Upregulating IL-1β and TNF-α

Wang

Sun

Tang

et al. 2021

Preprint

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Background1,2-Dichloroethane (1,2-DCE) is a synthetic organic chemical that causes brain edema under subacute poisoning. Our previous studies indicated that the neuroinflammation could be induced due to activation of both astrocytes and microglia during the course of brain edema in 1,2-DCE intoxicated mice. However, the crosstalk between the two glial cells in 1,2-DCE-induced neuroinflammation is unclear. In the current studies, we hypothesized that astrocytes are the first responder to the effects of 1,2-DCE in the brain, as they adhere to the cerebral capillaries, and they are an essential component of the blood-brain barrier (BBB).MethodsWe used primary cultured rat astrocytes and microglia, as well as a highly aggressively proliferating immortalized (HAPI) microglia cell line to study the effects of astrocytes on microglia polarization following exposure to 2-CE. ResultsFindings from the present studies demonstrated that treatment of primary rat astrocytes with 2-chloroethanol (2-CE), the intermediate metabolite of 1,2-DCE in vivo, can stimulate the activation of A1 reactive astrocytes (A1s) through p38 mitogen-activated protein kinase (p38 MAPK)/ nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) signaling pathways by the reactive oxygen species (ROS) produced during 2-CE metabolism. A1s activated by 2-CE can upregulate the expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), and stimulate the M1 polarization of microglia through IL-1β and TNF-α released by 2-CE activated A1s. Microglia are less sensitive to 2-CE than astrocytes, since treatment of primary rat microglia with 30 mM 2-CE alone failed to activate them, though this dose of 2-CE can activate A1s and in turn stimulate M1 polarization of microglia through the factors released by A1s. ConclusionThe neuroinflammation induced by 1,2-DCE in the brain of mice is most probably triggered by the activation of astrocytes. The understanding of the multidimensional roles of reactive astrocytes may further the development of new treatment strategies in reducing neuroinflammation and brain edema following 1,2-DCE-induced toxic encephalopathy.

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Fluorocitrate induced the alterations of memory-related proteins and tau hyperphosphorylation in SD rats

Cited by 13 publications

References 33 publications

In Vitro Astroglial Dysfunction Induced by Neurotoxins: Mimicking Astrocytic Metabolic Alterations of Alzheimer’s Disease

In Vitro Astroglial Dysfunction Induced by Neurotoxins: Mimicking Astrocytic Metabolic Alterations of Alzheimer’s Disease

S100B Secretion in Astrocytes, Unlike C6 Glioma Cells, Is Downregulated by Lactate

A1 Reactive Astrocytes Activated by 2-chloroethanol Modulate M1 Microglia Polarization through Upregulating IL-1β and TNF-α

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