Inhibition of Reactive Astrocytes with Fluorocitrate Ameliorates Learning and Memory Impairment Through Upregulating CRTC1 and Synaptophysin in Ischemic Stroke Rats

Zhang, Xinyu; Shen, Xiaoye; Dong, Jing; Liu, Wen-Cao; Song, Min Kyung; Sun, Yuanheng; Shu, Hui; Towse, Clare‐Louise; Liu, Wenlan; Liu, Chunfeng; Jin, Xinchun

doi:10.1007/s10571-019-00709-0

Cited by 32 publications

(23 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These neuroplasticity genes include, among others, the neurotrophic factor Bdnf, the immediate-early genes c-fos, Zif268/Egr1, and Arc, the orphan nuclear receptors Nr4a1 and Nr4a2, the brainspecific growth factor Fgf1, and autophagy genes involved in synaptic turnover and late-phase long-term synaptic depression (Zhou et al, 2006;Espana et al, 2010;Breuillaud et al, 2012;Ch'ng et al, 2012Ch'ng et al, , 2015Nonaka et al, 2014;Parra-Damas et al, 2014, 2017aFukuchi et al, 2015;Uchida et al, 2017;Pan et al, 2021). In agreement with CRTC1's role in the induction of these neuroplasticity genes, accumulating evidence supports its involvement in neuronal plasticity processes, such as activityand BDNF-induced dendritic growth of developing cortical neurons (Li et al, 2009;Finsterwald et al, 2010), maintenance of hippocampal late-phase LTP (Zhou et al, 2006;Kovacs et al, 2007;Uchida et al, 2017), and long-term memory formation (Sekeres et al, 2012;Nonaka et al, 2014;Parra-Damas et al, 2014, 2017aUchida et al, 2017;Zhang et al, 2019;Shu et al, 2020;Yan et al, 2021). Of particular importance, increasing evidence suggests that CRTC1 dysregulation may be implicated in the etiopathogenesis of neurodegenerative diseases, such as Huntington's, Parkinson's, and Alzheimer's disease, as well as psychiatric disorders (Boulting et al, 2021), including mood disorders [reviewed in Saura and Cardinaux (2017)].…”

Section: Creb-regulated Transcription Coactivator 1 In Brain Function...mentioning

confidence: 80%

New Insights Into the Pivotal Role of CREB-Regulated Transcription Coactivator 1 in Depression and Comorbid Obesity

Rossetti

Cherix

Guiraud

et al. 2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Depression and obesity are major public health concerns, and there is mounting evidence that they share etiopathophysiological mechanisms. The neurobiological pathways involved in both mood and energy balance regulation are complex, multifactorial and still incompletely understood. As a coactivator of the pleiotropic transcription factor cAMP response element-binding protein (CREB), CREB-regulated transcription coactivator 1 (CRTC1) has recently emerged as a novel regulator of neuronal plasticity and brain functions, while CRTC1 dysfunction has been associated with neurodegenerative and psychiatric diseases. This review focuses on recent evidence emphasizing the critical role of CRTC1 in the neurobiology of depression and comorbid obesity. We discuss the role of CRTC1 downregulation in mediating chronic stress-induced depressive-like behaviors, and antidepressant response in the light of the previously characterized Crtc1 knockout mouse model of depression. The putative role of CRTC1 in the alteration of brain energy homeostasis observed in depression is also discussed. Finally, we highlight rodent and human studies supporting the critical involvement of CRTC1 in depression-associated obesity.

show abstract

Section: Creb-regulated Transcription Coactivator 1 In Brain Function...mentioning

confidence: 80%

New Insights Into the Pivotal Role of CREB-Regulated Transcription Coactivator 1 in Depression and Comorbid Obesity

Rossetti

Cherix

Guiraud

et al. 2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…It is apparent that aberrant synaptic plasticity, due to abnormal expression of synaptophysin and the postsynaptic scaffolding protein, PSD-95, in the hippocampus, is functionally related to cognitive decline and Alzheimer's Disease [75][76][77]. The loss of pre/post synaptic proteins, progressive loss of synaptic density and the subsequent cognitive decline is typi ed by an increase in reactive astrocytic expression, alongside microglial activation [78,79]. We, and others, have demonstrated that CS exposure induces a loss of synaptic integrity, via a reduction in synaptophysin in the hilus region of the dentate gyrus [80] and importantly this is not reversible even after 33 days CS cessation.…”

Section: Discussionmentioning

confidence: 99%

Ebselen Prevents Cigarette Smoke-Induced Cognitive Dysfunction In Mice By Preserving Hippocampal Synaptophysin Expression

Luca

Brassington

Chan

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Cigarette smoking (CS) is the leading cause of chronic obstructive pulmonary disease (COPD). The “spill-over” of pulmonary inflammation into the systemic circulation may damage the brain, leading to cognitive dysfunction. Cessation of CS can improve pulmonary and neurocognitive outcomes, however, its benefit on the neuroinflammatory profile remains uncertain. Here, we investigate how CS exposure impairs neurocognition and whether this can be reversed with CS cessation or an antioxidant treatment. Methods: Male BALB/c mice were exposed CS (9 cigarettes/day for 8 weeks) followed by 4 weeks of CS cessation. Another cohort of CS-exposed mice were co-administrated with a glutathione peroxidase (Gpx) mimetic, ebselen (10mg/kg) or vehicle (5% CM-cellulose). We assessed pulmonary inflammation, spatial and working memory, and the hippocampal microglial, oxidative and synaptic profiles. Results: CS exposure increased lung inflammation which was reduced following CS cessation. CS caused spatial and working memory impairments which were attributed to hippocampal microglial activation and suppression of synaptophysin. CS cessation did not improve memory deficits or alter microglial activation. Ebselen completely prevented the CS-induced working and spatial memory impairments, which was associated with restored synaptophysin expression without altering microglial activation.Conclusion: We were able to model the CS-induced memory impairment and microglial activation seen in human COPD. The preventative effects of ebselen on memory impairment is likely to be dependent on a preserved synaptogenic profile. Cessation alone also appears to be insufficient in correcting the memory impairment, suggesting the importance of incorporating antioxidant therapy to help maximizing the benefit of cessation.

show abstract

“…Immunostaining for CRTC1, HMGB1, Iba-1, NeuN, occludin, p-CREB The 20-μm-thick frozen slices were xed with 4 % PFA for further analysis as we described previously (Zhang et al 2019). In brief, the sections were blocked with 5 % goat serum for 2 h to inhibit nonspeci c binding and incubated with primary antibody against HMGB1 (1:800; Abcam, ab79823, UK), CRTC1…”

Section: Evaluation Of Bbb Permeability By Detection Of Immunoglobulin G Leakagementioning

confidence: 99%

Modulation of α7nAchR by Melatonin Alleviates Ischemia and Reperfusion-Compromised Integrity of Blood–Brain Barrier Through Inhibiting HMGB1-Mediated Microglia Activation and CRTC1-Mediated Neuronal Loss

Chen

Sun

et al. 2021

Cell Mol Neurobiol

Self Cite

View full text Add to dashboard Cite

The only food and drug administration (FDA)-approved drug currently available for the treatment of acute ischemic stroke is tissue plasminogen activator (tPA), yet the therapeutic bene ts of this drug are partially outweighed by the increased risk of hemorrhagic transformation (HT). Analysis of the NIH trial has shown that cigarette smoking protected tPA-treated patients from HT, however, the underlying mechanism is not clear. Nicotinic acetylcholine receptors (nAChR) has shown anti-in ammatory effect and modulation nAChR could be a strategy to reduce ischemia/reperfusion-induced blood brain barrier (BBB) damage. Since melatonin could regulate the expression of α7nAchR and melatonin's neuroprotective effect against ischemic injury is mediated via α7nAChR modulation, here, we aim to test the hypothesis that melatonin reduces ischemia and reperfusion (I/R)-induced BBB damage through modulation of α7nACh receptor (α7nAChR). Mice were subjected to 1.5 h ischemia and 24 h reperfusion and at the onset of reperfusion, mice received intraperitoneal administration (i.p.) of either drug or saline. Mice were randomly assigned into ve groups: Saline; α7nAChR agonist PNU282987; Melatonin; Melatonin + Methyllycaconitine (MLA, α7nAChR antagonist) and MLA group. BBB permeability was assessed by detecting the extravasation of Evan's blue and IgG. Our results showed that I/R signi cantly increased BBB permeability accompanied by occludin degradation, microglia activation, and high mobility group box 1 (HMGB1) release from the neuron. In addition, I/R signi cantly induced neuronal loss accompanied by the decrease of CREB regulated transcriptional coactivator 1 (CRTC1) and p-CREB expression. Melatonin treatment signi cantly inhibited the above changes through modulating α7nAChR. Taken together, these results demonstrate that melatonin provides a protective effect on ischemia/reperfusioninduced BBB damage, at least in part, depending on modulation of α7nAChR.

show abstract

Inhibition of Reactive Astrocytes with Fluorocitrate Ameliorates Learning and Memory Impairment Through Upregulating CRTC1 and Synaptophysin in Ischemic Stroke Rats

Cited by 32 publications

References 60 publications

New Insights Into the Pivotal Role of CREB-Regulated Transcription Coactivator 1 in Depression and Comorbid Obesity

New Insights Into the Pivotal Role of CREB-Regulated Transcription Coactivator 1 in Depression and Comorbid Obesity

Ebselen Prevents Cigarette Smoke-Induced Cognitive Dysfunction In Mice By Preserving Hippocampal Synaptophysin Expression

Modulation of α7nAchR by Melatonin Alleviates Ischemia and Reperfusion-Compromised Integrity of Blood–Brain Barrier Through Inhibiting HMGB1-Mediated Microglia Activation and CRTC1-Mediated Neuronal Loss

Contact Info

Product

Resources

About