STAT6 mediates the effect of ethanol on neuroinflammatory response in TBI

Heuvel, Florian olde; Holl, Sarah; Chandrasekar, Akila; Li, Zhenghui; Wang, Yibin; Rehman, Rida; Förstner, Philip; Sinske, Daniela; Palmer, Annette; Wiesner, Diana; Ludolph, Albert C.; Huber‐Lang, Markus; Relja, Borna; Wirth, Thomas; Röszer, Tamás; Baumann, Bernd; Boeckers, Tobias M.; Knöll, Bernd; Roselli, Francesco

doi:10.1016/j.bbi.2019.06.019

Cited by 37 publications

(55 citation statements)

References 93 publications

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“…Nevertheless, evidence of reduced GFAP immunoreactivity following traumatic brain injury (TBI) has been reported previously and is attributed to the breakdown of intermediate filaments and a concomitant alteration in overall protein function [36]. In light of TBI inducing glial activation and neuroinflammation in the hippocampus, it is possible that similar mechanism could underlie the reduced GFAP observed in the hippocampus in DSS-induced colitis model mice [37]. Furthermore, the decrease of astrocyte in the model group may be related to the suppression of antiinflammatory effect of hippocampal astrocyte; on the contrary, both EA and moxibustion could activate the GFAP expression in the hippocampus and contribute to the therapeutic effect on hippocampus inflammation.…”

Section: Discussionmentioning

confidence: 88%

Electroacupuncture and Moxibustion Regulate Hippocampus Glia and Mitochondria Activation in DSS‐Induced Colitis Mice

Zhang

Xie

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objectives. To study the influence of electroacupuncture (EA) and moxibustion on the hippocampus astrocyte and microglia activation in the ulcerative colitis model and to evaluate the mitochondria activity. Methods. 2.5% dextran sodium sulfate-induced colitis mice were treated by EA or moxibustion. Intestinal pathological structure was observed by hematoxylin and eosin (H&E) staining; the expression of GFAP or S100b (markers for astrocyte), Iba-1 (a marker for microglia), and Mitofilin (a marker for mitochondria) in hippocampus was detected by immunofluorescence staining or western blot. Results. The results demonstrated that both EA and moxibustion could improve the morphology of distal colonic mucosal epithelia in DSS-induced colitis mice. Expression of GFAP in the hippocampus was significantly increased after EA or moxibustion treatment. The effects were further supported by WB results. Meanwhile, expression of mitofilin in the hippocampus CA1 and CA3 regions showed the same trend as that of GFAP. Expression of Iba-1 in the hippocampus showed no significant difference after EA or moxibustion treatment, while the state of microglia changed from resting in control mice to activated state in colitis mice. Conclusion. EA and moxibustion were able to modulate the activation of astrocyte, microglial, and mitochondria in the hippocampus area in the colitis model.

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Section: Discussionmentioning

confidence: 88%

Electroacupuncture and Moxibustion Regulate Hippocampus Glia and Mitochondria Activation in DSS‐Induced Colitis Mice

Zhang

Xie

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…For cortical tissue (Figure M), the ΔΔCt method was applied to provide the fold change of mRNA level as follows: 2 −(ΔCt TBI ipsi − ΔCt sham ipsi) . Primer sequences were reported earlier or can be provided upon request …”

Section: Methodsmentioning

confidence: 99%

Interference of neuronal activity‐mediated gene expression through serum response factor deletion enhances mortality and hyperactivity after traumatic brain injury

Förstner

Knöll

2020

FASEB j.

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Traumatic brain injury (TBI) is one of the most frequent causes of brain injury and mortality in young adults with detrimental sequelae such as cognitive impairments, epilepsy, and attention‐deficit hyperactivity disorder. TBI modulates the neuronal excitability resulting in propagation of a neuronal activity‐driven gene expression program. However, the impact of such neuronal activity mediated gene expression in TBI has been poorly studied. In this study we analyzed mouse mutants of the prototypical neuronal activity‐dependent transcription factor SRF (serum response factor) in a weight‐drop TBI model. Neuron‐restricted SRF deletion elevated TBI inflicted mortality suggesting a neuroprotective SRF function during TBI. Behavioral inspection uncovered elevated locomotor activity in Srf mutant mice after TBI in contrast to hypoactivity observed in wild‐type littermates. This indicates an SRF role in modulation of TBI‐associated alterations in locomotor activity. Finally, induction of a neuronal activity induced gene expression program composed of immediate early genes (IEGs) such as Egr1, Egr2, Egr3, Npas4, Atf3, Arc, Ptgs2, and neuronal pentraxins (Nptx2) was compromised upon SRF depletion. Overall, our data show a role of neuronal activity‐mediated gene transcription during TBI and suggest a molecular link between TBI and such post‐TBI neurological comorbidities involving hyperactivity phenotypes.

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“…Detection of mRNA in situ together with co-immunostaining was performed as previously reported ( Olde Heuvel et al, 2019 ) and according to the manufacturer’s recommendation (Acd Bio). Details of the procedure are reported in , and details of the probes used are reported in Table S1.…”

Section: Methodsmentioning

confidence: 99%

“…For the preparation of whole spinal cord protein extract, the lumbar spinal cord was dissected after mouse euthanasia by cervical dislocation and snap frozen on dry ice as previously reported (Olde Heuvel et al, 2019). Briefly, lumbar spinal cord tissue was dissected and homogenized in a complete radioimmunoprecipitation assay (RIPA) buffer, containing protease and phosphatase inhibitors.…”

Section: Western Blotmentioning

confidence: 99%

Multiplexed chemogenetics in astrocytes and motoneurons restore blood–spinal cord barrier in ALS

et al. 2020

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Blood–spinal cord barrier (BSCB) disruption is thought to contribute to motoneuron (MN) loss in amyotrophic lateral sclerosis (ALS). It is currently unclear whether impairment of the BSCB is the cause or consequence of MN dysfunction and whether its restoration may be directly beneficial. We revealed that SOD1G93A, FUSΔNLS, TDP43G298S, and Tbk1+/− ALS mouse models commonly shared alterations in the BSCB, unrelated to motoneuron loss. We exploit PSAM/PSEM chemogenetics in SOD1G93A mice to demonstrate that the BSCB is rescued by increased MN firing, whereas inactivation worsens it. Moreover, we use DREADD chemogenetics, alone or in multiplexed form, to show that activation of Gi signaling in astrocytes restores BSCB integrity, independently of MN firing, with no effect on MN disease markers and dissociating them from BSCB disruption. We show that astrocytic levels of the BSCB stabilizers Wnt7a and Wnt5a are decreased in SOD1G93A mice and strongly enhanced by Gi signaling, although further decreased by MN inactivation. Thus, we demonstrate that BSCB impairment follows MN dysfunction in ALS pathogenesis but can be reversed by Gi-induced expression of astrocytic Wnt5a/7a.

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STAT6 mediates the effect of ethanol on neuroinflammatory response in TBI

Cited by 37 publications

References 93 publications

Electroacupuncture and Moxibustion Regulate Hippocampus Glia and Mitochondria Activation in DSS‐Induced Colitis Mice

Electroacupuncture and Moxibustion Regulate Hippocampus Glia and Mitochondria Activation in DSS‐Induced Colitis Mice

Interference of neuronal activity‐mediated gene expression through serum response factor deletion enhances mortality and hyperactivity after traumatic brain injury

Multiplexed chemogenetics in astrocytes and motoneurons restore blood–spinal cord barrier in ALS

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