The critical role of lipopolysaccharide in the upregulation of aquaporin 4 in glial cells treated with Shiga toxin

Sugimoto, Naotoshi; Leu, Hue; Inoue, Natsumi; Shimizu, Masaki; Toma, Tomoko; Kuroda, Masashi; Saito, Tatsuhito; Wada, Taizo; Yachie, Akihiro

doi:10.1186/s12929-015-0184-5

Cited by 18 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are, however, other reports stating that overexpression of AQP4 in astrocytes causes their swelling and disturbs brain homeostasis (Sugimoto et al. ), whereas reduction of the protein contents is beneficial for maintaining proper brain osmolarity, which also confirms propitious effects of LPS pretreatments.…”

Section: Discussionmentioning

confidence: 88%

Inflammation in the developing rat modulates astroglial reactivity to seizures in the mature brain

2017

View full text Add to dashboard Cite

Astrocytes participate in neuronal development and excitability, and produce factors enhancing or suppressing inflammatory processes occurring due to neurodegenerative diseases, such as epilepsy. Seizures, in turn, trigger the release of inflammatory mediators, causing structural and functional changes in the brain. Therefore, it appears reasonable to determine whether generalized inflammation at developmental periods can affect astrocyte reactivity to epileptic seizures occurring in the adult brain. Lipopolysaccharide (LPS) was injected in 6- or 30-day-old rats (P6 or P30, respectively). At the age of 2 months, seizures were induced, and pilocarpine and morphological changes of astrocytes located within the hippocampal formation were assessed. Additionally, expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), aquaporin 4 (AQP4), and inwardly rectifying potassium channel Kir 4.1 (Kir4.1) was determined using Western blots. The animal group given LPS on P6 displayed maximal susceptibility to pilocarpine-induced seizures, significantly higher than the group that received LPS on P30. In the immunohistologically examined hippocampal formation, the GFAP-immunoreactive area was not affected by LPS alone. However, it was reduced following seizures in naïve controls but not in LPS-pretreated rats. Increases in the ramification of astrocytic processes were detected only in adult rats given LPS on P30, not on P6. Seizures abolished the effects. Following seizures, the process ramification showed no significant change in the two LPS-treated rat groups, whereas it was significantly reduced in the dentate gyrus of LPS-untreated controls. Glial fibrillary acidic protein (GFAP) expression showed no changes induced with LPS alone and rose slightly after seizures. AQP4 content was lower in rats given LPS on P6 and was seizure-resistant in the two LPS-treated groups, contrary to a decrease in untreated controls. GS expression was not affected by LPS treatments and was reduced after seizures without an intergroup difference. Kir4.1 underwent highly significant increases in all groups experiencing seizures, but LPS alone had no effect. It can be concluded that the generalized inflammatory status led to some important changes in astrocytes reflected, in part at least by permanent modifications of their morphology and molecular profile. Moreover, the previously experienced inflammation prevented the cells from much stronger changes in response to seizures observed in adult untreated controls. The obtained results point to a link between the activation of astrocytes by transient systemic inflammation occurring during the developmental period and their subsequent reactivity to seizures, which may play an important role in the functional features of the brain, including its susceptibility to seizures.

show abstract

Section: Discussionmentioning

confidence: 88%

Inflammation in the developing rat modulates astroglial reactivity to seizures in the mature brain

2017

View full text Add to dashboard Cite

show abstract

“…In our mice, we tried to elucidate other possible mechanisms behind our observed effect on CSF movement. AQP4-expression and polarization in astrocytic endfeet have been shown to be key factors for CSF tracer dynamics [ 29 ], as well as to be affected after a neuroinflammatory stimuli [ 32 ], such as LPS [ 33 ]. Thus, we measured both AQP4 expression and polarization, but could not find any indication that our acute effects of LPS were caused by changes to this water channel.…”

Section: Discussionmentioning

confidence: 99%

Acute systemic LPS-exposure impairs perivascular CSF distribution in mice

Manouchehrian

Ramos

Bachiller

et al. 2021

J Neuroinflammation

View full text Add to dashboard Cite

Background The exchange of cerebrospinal (CSF) and interstitial fluid is believed to be vital for waste clearance in the brain. The sleep-dependent glymphatic system, which is comprised of perivascular flow of CSF and is largely dependent on arterial pulsatility and astrocytic aquaporin-4 (AQP4) expression, facilitates much of this brain clearance. During the last decade, several observations have indicated that impaired glymphatic function goes hand in hand with neurodegenerative diseases. Since pathologies of the brain carry inflammatory components, we wanted to know how acute inflammation, e.g., with lipopolysaccharide (LPS) injections, would affect the glymphatic system. In this study, we aim to measure the effect of LPS on perivascular CSF distribution as a measure of glymphatic function. Methods Three hours after injection of LPS (1 mg/kg i.p.), C57bl/6 mice were (1) imaged for two CSF tracers, injected into cisterna magna, (2) transcardially perfused with buffer, or (3) used for physiological readouts. Tracer flow was imaged using a low magnification microscope on fixed brains, as well as using vibratome-cut slices for measuring tracer penetration in the brain. Cytokines, glial, and BBB-permeability markers were measured with ELISAs, Western blots, and immunohistochemistry. Cerebral blood flow was approximated using laser Doppler flowmetry, respiration and heart rate with a surgical monitor, and AQP4-polarization was quantified using confocal microscopy of immunolabeled brain sections. Results LPS-injections significantly lowered perivascular CSF tracer flow and penetration into the parenchyma. No differences in AQP4 polarization, cytokines, astroglial and BBB markers, cerebral blood flow, or respiration were detected in LPS-injected mice, although LPS did elevate cortical Iba1+ area and heart rate. Conclusions This study reports another physiological response after acute exposure to the bacterial endotoxin LPS, namely the statistically significant decrease in perivascular distribution of CSF. These observations may benefit our understanding of the role of systemic inflammation in brain clearance.

show abstract

“…Specific aquaporins may be upregulated or downregulated in response to LPS administration suggesting they may play a role in sepsis pathogenesis [71]. LPS, shiga toxin and cholera toxin have all been shown to alter aquaporin expression [72,73]. Aquaporins can enhance immune cell migration via water influx to facilitate actin remodeling at the leading edge of the cell; like AQP9 acting in neutrophils [74,75].…”

Section: Selected Bacterial Pampsmentioning

confidence: 99%

Inflammatory Response to Different Toxins in Experimental Sepsis Models

Dickson

Lehmann

2019

IJMS

164

128

View full text Add to dashboard Cite

Sepsis is defined as life-threatening organ dysfunction caused by the dysregulated host response to infection. Despite serious mortality and morbidity, no sepsis-specific drugs exist. Endotoxemia is often used to model the hyperinflammation associated with early sepsis. This model classically uses lipopolysaccharide (LPS) from Gram-negative pathogens to activate the immune system, leading to hyperinflammation, microcirculatory disturbances and death. Other toxins may also be used to activate the immune system including Gram-positive peptidoglycan (PG) and lipoteichoic acid (LTA). In addition to these standard toxins, other bacterial components can induce inflammation. These molecules activate different signaling pathways and produce different physiological responses which can be taken advantage of for sepsis modeling. Endotoxemia modeling can provide information on pathways to inflammation in sepsis and contribute to preclinical drug development.

show abstract

The critical role of lipopolysaccharide in the upregulation of aquaporin 4 in glial cells treated with Shiga toxin

Cited by 18 publications

References 36 publications

Inflammation in the developing rat modulates astroglial reactivity to seizures in the mature brain

Inflammation in the developing rat modulates astroglial reactivity to seizures in the mature brain

Acute systemic LPS-exposure impairs perivascular CSF distribution in mice

Inflammatory Response to Different Toxins in Experimental Sepsis Models

Contact Info

Product

Resources

About