The Nuclear Calcium Signaling Target, Activating Transcription Factor 3 (ATF3), Protects against Dendrotoxicity and Facilitates the Recovery of Synaptic Transmission after an Excitotoxic Insult

Ahlgren, Hanna; Bas‐Orth, Carlos; Freitag, H. Eckehard; Hellwig, Andrea; Ottersen, Ole Petter; Bading, Hilmar

doi:10.1074/jbc.m113.502914

Cited by 45 publications

(38 citation statements)

References 67 publications

(123 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2,3 The mechanisms underlying increased resilience are not fully understood for all genes, but shielding mitochondria against excitotoxic damage induced by extrasynaptic NMDA receptors and protecting structural integrity and cellular bioenergetics are emerging common themes. 2,[4][5][6][7][8][9] Overexpression of each AID gene using recombinant adeno-associated viruses (rAAVs) provides effective protection against apoptotic cell death in cultured hippocampal neurons and neurodegeneration in vivo induced by kainate-induced seizures. 1,2 Moreover, expression of Atf3 and Inhba, also known as Activin A, reduces brain damage caused by ischemic conditions following middle cerebral artery occlusion (MCAO) in the mouse.…”

Section: Introductionmentioning

confidence: 99%

Post-injury Nose-to-Brain Delivery of Activin A and SerpinB2 Reduces Brain Damage in a Mouse Stroke Model

2018

Self Cite

View full text Add to dashboard Cite

Synaptic NMDA receptors activating nuclear calcium-driven adaptogenomics control a potent body-own neuroprotective mechanism, referred to as acquired neuroprotection. Viral vector-mediated gene transfer in conjunction with stereotactic surgery has previously demonstrated the proficiency of several nuclear calcium-regulated genes to protect in vivo against brain damage caused by toxic extrasynaptic NMDA receptor signaling following seizures or stroke. Here we used noninvasive nose-to-brain administration of Activin A and SerpinB2, two secreted nuclear calcium-regulated neuroprotectants, for post-injury treatment of brain damage following middle cerebral artery occlusion (MCAO) in C57BL/6N mice. The observed reduction of the infarct volume was comparable to the protection obtained by intracerebroventricular injection of recombinant Activin A or SerpinB2 or by stereotactic delivery 3 weeks prior to the injury of a recombinant adeno-associated virus containing an expression cassette for the potent neuroprotective transcription factor Npas4. These results establish post-injury, nose-to-brain delivery of Activin A and SerpinB2 as effective and possibly clinically applicable treatments of acute and chronic neurodegenerative conditions.

show abstract

Section: Introductionmentioning

confidence: 99%

Post-injury Nose-to-Brain Delivery of Activin A and SerpinB2 Reduces Brain Damage in a Mouse Stroke Model

2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…[ 33 ] ATF3 expression and synaptic activity promote resistance of hippocampal neurons to loss of synapses and acute dendrotoxicity, which contributes to functional restoration of neuronal networks after excitotoxic insults. [ 34 ] Therefore, ATF3 may have an important protective effect in IS.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of gene expression profiling for identification of potential key genes among ischemic stroke

et al. 2017

View full text Add to dashboard Cite

This study aimed to identify the key differentially expressed genes (DEGs) following ischemic stroke (IS).The GSE22255 microarray dataset, which contains samples from peripheral blood mononuclear cells of 20 IS patients and 20 sex- and age-matched controls, was downloaded from the Gene Expression Omnibus. After data pre-processing, DEGs were identified using the Linear Models for Microarray Data package in R. The Search Tool for the Retrieval of Interacting Genes database was used to predict the interactions among the products of DEGs, and then Cytoscape software was used to visualize the protein–protein interaction (PPI) network. DEGs in the PPI network were then analyzed using the Database for Annotation, Visualization, and Integrated Discovery online software to predict their underlying functions through functional and pathway enrichment analyses.A total of 144 DEGs were identified in IS samples compared with control samples, including 75 upregulated and 69 downregulated genes. Genes with higher degrees in the PPI network included FOS (degree = 26), TP53 (degree = 22), JUN (degree = 20), EGR1 (degree = 18), JUNB (degree = 16), and ATF3 (degree = 15), and these genes may function in IS by interacting with each other (e.g., EGR1-JUN, EGR1-TP53, ATF3-FOS, and JUNB-FOS). Functional enrichment analysis indicated that the downregulated TP53 gene was enriched in immune response and protein targeting categories.ATF3 and EGR1 may have an important protective effect on IS, whereas FOS, JUN, and JUNB may be associated with the development of IS. In addition, TP53 may function as an indicator of poor prognosis for IS through its association with the immune response and protein targeting.

show abstract

“…The dendritic beading, focal or varicose swellings of dendritic arbors, has been regarded as a morphological hallmark of neuronal injury and dendrotoxicity (Ahlgren et al, 2014; Al-Noori and Swann, 2000) and regularly-spaced and spherical dendritic varicosities may be Ca2+-independent (Hoskison et al, 2007). Our data showed this dendritic beading was frequently observed in hippocampus of rabbits fed with 2% cholesterol but absent in normal chow fed rabbits.…”

Section: Discussionmentioning

confidence: 99%

Dietary cholesterol concentration affects synaptic plasticity and dendrite spine morphology of rabbit hippocampal neurons

Wang

Zheng

2015

Brain Research

View full text Add to dashboard Cite

Previous studies have shown dietary cholesterol can enhance learning but retard memory which may be partly due to increased cholesterol levels in hippocampus and reduced afterhyperpolarization (AHP) amplitude of hippocampal CA1 neurons. This study explored the dose-dependent effect of dietary cholesterol on synaptic plasticity of rabbit hippocampal CA1 neurons and spine morphology, the postsynaptic structures responsible for synaptic plasticity. Field potential recordings revealed a low concentration of dietary cholesterol increased long-term potentiation (LTP) expression while high concentrations produced a pronounced reduction in LTP expression. Dietary cholesterol facilitated basal synaptic transmission but did not influence presynaptic function. DiI staining showed dietary cholesterol induced alterations in dendrite spine morphology characterized by increased mushroom spine density and decreased thin spine density, two kinds of dendritic spines that may be linked to memory consolidation and learning acquisition. Dietary cholesterol also modulated the geometric measures of mushroom spines. Therefore, dietary cholesterol dose-dependently modulated both synaptic plasticity and dendrite spine morphologies of hippocampal CA1 neurons that could mediate learning and memory changes previously seen to result from feeding a cholesterol diet.

show abstract

The Nuclear Calcium Signaling Target, Activating Transcription Factor 3 (ATF3), Protects against Dendrotoxicity and Facilitates the Recovery of Synaptic Transmission after an Excitotoxic Insult

Cited by 45 publications

References 67 publications

Post-injury Nose-to-Brain Delivery of Activin A and SerpinB2 Reduces Brain Damage in a Mouse Stroke Model

Post-injury Nose-to-Brain Delivery of Activin A and SerpinB2 Reduces Brain Damage in a Mouse Stroke Model

Bioinformatics analysis of gene expression profiling for identification of potential key genes among ischemic stroke

Dietary cholesterol concentration affects synaptic plasticity and dendrite spine morphology of rabbit hippocampal neurons

Contact Info

Product

Resources

About