ERK and p38 inhibitors attenuate memory deficits and increase CREB phosphorylation and PGC-1α levels in Aβ-injected rats

Ashabi, Ghorbangol; Ramin, Mahmoudreza; Azizi, Parisa; Taslimi, Zahra; Alamdary, Shabnam Zeighamy; Haghparast, Abbas; Ansari, Niloufar; Motamedi, Fereshteh; Khodagholi, Fariba

doi:10.1016/j.bbr.2012.04.006

Cited by 53 publications

(23 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the knockdown of PGC-1α inhibited spinogenesis and synaptogenesis in cultured hippocampal neurons (Cheng et al, 2012) and hippocampal neuritogenesis may be associated with the formation of trace memories (Shors, 2004), one may suggest that hippocampal increase of PGC-1α is involved in passive avoidance learning. This hypothesis can be supported by the findings which suggested that the levels of the PGC-1α and its down streams were reduced in Alzheimer disease (Ashabi et al, 2012). Moreover, our results also indicated that 30 min exposure to acute stress decreased the hippocampal levels of PGC-1α, NRF-1 and TFAM.…”

Section: Discussionsupporting

confidence: 87%

Hippocampal signaling pathways are involved in stress-induced impairment of memory formation in rats

2015

Self Cite

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 87%

Hippocampal signaling pathways are involved in stress-induced impairment of memory formation in rats

2015

Self Cite

View full text Add to dashboard Cite

“…MEK/ERK signaling has been implicated as a negative regulator of both PGC-1a and MB. Pharmacologic inhibition of MEK reversed reductions in protein levels of PGC-1a and downstream regulators of MB (NRF-1, TFAM) in the hippocampi of rats receiving intracerebroventricular injections of amyloid-b (Ashabi et al, 2012). In addition, blockade of ERK activation prevented palmitate-induced downregulation of PGC-1a in skeletal muscle myotubes in vitro (Coll et al, 2006).…”

Section: Discussionmentioning

confidence: 93%

“…TLR4 is known to initiate signaling by a number of different mediators, most notably nuclear factor kB (NF-kB) and members of the mitogenactivated protein kinase (MAPK) family, including extracellular signal-related kinases 1/2 (ERK1/2), p38 MAPKs, and c-Jun N-terminal kinases (Ostuni et al, 2010;Lin and Tang, 2014). Previous studies showed that ERK1/2 activation may negatively regulate expression of PGC-1a in multiple organs including the brain and skeletal muscle (Coll et al, 2006;Ashabi et al, 2012). In addition, TPL-2 is thought to be critical for activation of ERK1/2 in response to LPS (Dumitru et al, 2000;Banerjee et al, 2006).…”

Section: Resultsmentioning

confidence: 99%

Suppression of Mitochondrial Biogenesis through Toll-Like Receptor 4–Dependent Mitogen-Activated Protein Kinase Kinase/Extracellular Signal-Regulated Kinase Signaling in Endotoxin-Induced Acute Kidney Injury

Smith

Stallons

Collier

et al. 2014

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Although disruption of mitochondrial homeostasis and biogenesis (MB) is a widely accepted pathophysiologic feature of sepsisinduced acute kidney injury (AKI), the molecular mechanisms responsible for this phenomenon are unknown. In this study, we examined the signaling pathways responsible for the suppression of MB in a mouse model of lipopolysaccharide (LPS)-induced AKI. Downregulation of peroxisome proliferator-activated receptor g coactivator-1a (PGC-1a), a master regulator of MB, was noted at the mRNA level at 3 hours and protein level at 18 hours in the renal cortex, and was associated with loss of renal function after LPS treatment. LPS-mediated suppression of PGC-1a led to reduced expression of downstream regulators of MB and electron transport chain proteins along with a reduction in renal cortical mitochondrial DNA content. Mechanistically, Toll-like receptor 4 (TLR4) knockout mice were protected from renal injury and disruption of MB after LPS exposure. Immunoblot analysis revealed activation of tumor progression locus 2/mitogen-activated protein kinase kinase/ extracellular signal-regulated kinase (TPL-2/MEK/ERK) signaling in the renal cortex by LPS. Pharmacologic inhibition of MEK/ ERK signaling attenuated renal dysfunction and loss of PGC-1a, and was associated with a reduction in proinflammatory cytokine (e.g., tumor necrosis factor-a [TNF-a], interleukin-1b) expression at 3 hours after LPS exposure. Neutralization of TNF-a also blocked PGC-1a suppression, but not renal dysfunction, after LPS-induced AKI. Finally, systemic administration of recombinant tumor necrosis factor-a alone was sufficient to produce AKI and disrupt mitochondrial homeostasis. These findings indicate an important role for the TLR4/MEK/ERK pathway in both LPS-induced renal dysfunction and suppression of MB. TLR4/MEK/ERK/TNF-a signaling may represent a novel therapeutic target to prevent mitochondrial dysfunction and AKI produced by sepsis.

show abstract

“…The dosage of U0126 followed that in previous studies with some modification [22, 23]. Rats in TBI+SEW+U0126 group were not only treated with i.p.…”

Section: Methodsmentioning

confidence: 99%

Activation of Sphingosine 1-Phosphate Receptor 1 Enhances Hippocampus Neurogenesis in a Rat Model of Traumatic Brain Injury: An Involvement of MEK/Erk Signaling Pathway

Zhao

et al. 2016

Neural Plasticity

View full text Add to dashboard Cite

Among sphingosine 1-phosphate receptors (S1PRs) family, S1PR1 has been shown to be the most highly expressed subtype in neural stem cells (NSCs) and plays a crucial role in the migratory property of NSCs. Recent studies suggested that S1PR1 was expressed abundantly in the hippocampus, a specific neurogenic region in rodent brain for endogenous neurogenesis throughout life. However, the potential association between S1PR1 and neurogenesis in hippocampus following traumatic brain injury (TBI) remains unknown. In this study, the changes of hippocampal S1PR1 expression after TBI and their effects on neurogenesis and neurocognitive function were investigated, focusing on particularly the extracellular signal-regulated kinase (Erk) signaling pathway which had been found to regulate multiple properties of NSCs. The results showed that a marked upregulation of S1PR1 occurred with a peak at 7 days after trauma, revealing an enhancement of proliferation and neuronal differentiation of NSCs in hippocampus due to S1PR1 activation. More importantly, it was suggested that mitogen-activated protein kinase-Erk kinase (MEK)/Erk cascade was required for S1PR1-meidated neurogenesis and neurocognitive recovery following TBI. This study lays a preliminary foundation for future research on promoting hippocampal neurogenesis and improving TBI outcome.

show abstract

ERK and p38 inhibitors attenuate memory deficits and increase CREB phosphorylation and PGC-1α levels in Aβ-injected rats

Cited by 53 publications

References 64 publications

Hippocampal signaling pathways are involved in stress-induced impairment of memory formation in rats

Hippocampal signaling pathways are involved in stress-induced impairment of memory formation in rats

Suppression of Mitochondrial Biogenesis through Toll-Like Receptor 4–Dependent Mitogen-Activated Protein Kinase Kinase/Extracellular Signal-Regulated Kinase Signaling in Endotoxin-Induced Acute Kidney Injury

Activation of Sphingosine 1-Phosphate Receptor 1 Enhances Hippocampus Neurogenesis in a Rat Model of Traumatic Brain Injury: An Involvement of MEK/Erk Signaling Pathway

Contact Info

Product

Resources

About