Insulin protects against Aβ-induced spatial memory impairment, hippocampal apoptosis and MAPKs signaling disruption

Ghasemi, Rasoul; Zarifkar, Asadollah; Rastegar, Karim; Maghsoudi, Nader; Moosavi, Maryam

doi:10.1016/j.neuropharm.2014.01.036

Cited by 64 publications

(38 citation statements)

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“…Consistently, in vitro studies have shown that Aβ is toxic to neural cells (Loo et al 1993). Some studies proposed that Akt and ERK (extracellular signal-regulated kinases) are involved in Aβ toxicity both in animal models (Ghasemi et al 2014) and hippocampal slices (Chong et al 2006, Nassif et al 2007.…”

Section: Introductionmentioning

confidence: 80%

The Interplay of Akt and ERK in Aβ Toxicity and Insulin-Mediated Protection in Primary Hippocampal Cell Culture

et al. 2015

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It is not known if insulin prevents Aβ-induced cell death, MAPK, and Akt activity in isolated hippocampal cell culture. This study was aimed to explore the effect of insulin on Aβ-induced cell death and ERK and Akt signaling alteration in isolated hippocampal cell culture. Additionally, it was desirable to assess if there is any interaction between these two pathways. The hippocampal cells were derived from fetuses at the embryonic day 18-19. The cells were treated with different drugs, and MTT assay, morphological assessments, and Western blot were done. Insulin prevented Aβ-induced cell death and caspase-3 cleavage. Aβ-induced toxicity was aligned with decrement of the phosphorylated Akt (pAkt) which was prevented by insulin. The PI3 kinase inhibitor, LY294002, decreased pAkt and abolished the protective effect of insulin. Aβ exposure increased phosphorylated ERK (pERK) in parallel with cell death and apoptosis. Insulin-inhibited ERK activation (phosphorylation) induced by Aβ and PD98059 (as ERK inhibitor) did not affect the protective effect of insulin. One of the interesting finding of this study was the interplay of Akt and ERK in Aβ toxicity and insulin-mediated protection; meaning that there is an inverse relation between pERK and pAkt, in a way that PI3-Akt pathway inhibition leads to pERK increment while ERK inhibition causes Akt phosphorylation (activation). This study showed, for the first time, that insulin protects against Aβ toxicity in isolated hippocampal cell culture via modulating Akt and ERK phosphorylation and also revealed an interaction between those signals in Aβ toxicity and insulin-mediated protection.

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Section: Introductionmentioning

confidence: 80%

The Interplay of Akt and ERK in Aβ Toxicity and Insulin-Mediated Protection in Primary Hippocampal Cell Culture

et al. 2015

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“…It is one of the important signal transduction pathways of apoptosis induced by ischemia reperfusion injury (8). p-p38 MAPK activates the transcription factorsin downstream and caspase family members (Caspase-3, -6 and -7) (24).…”

Section: Discussionmentioning

confidence: 99%

“…The family members are a group of evolutionarily conserved enzymes in mammalian cells, including four subclasses: ERK1/2, JNK, p38 and ERK5 (7). In recent years, the MAPK family has been found to be an important signal-regulating enzyme between cell surface receptors and determinants of gene expression (8). Therefore, the MAPK family governs almost all the physiological functions and processes such as cell adaptation, proliferation, differentiation, survival, and programmed cell death.…”

Section: Introductionmentioning

confidence: 99%

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Protective effect of vitexin reduces sevoflurane-induced neuronal apoptosis through HIF-1α, VEGF and p38 MAPK signaling pathway inï¿½vitro and in newborn rats

et al. 2018

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Abstract. Previous studies have demonstrated thatVitexin possesses antihypertensive, anti-inflammatory and potential anticancer effects. The present study aimed to investigate whether the protective effect of vitexin protects against sevoflurane-induced neuronal apoptosis and the underlying mechanisms of this protective effect. The results demonstrated that Vitexin pretreatment significantly reduced neuronal apoptosis, and inhibited caspase-3 activity, apoptosis regulator BAX protein expression and malondialdehyde levels in sevoflurane-induced newborn rats. In addition, Vitexin pretreatment increased superoxide dismutase and glutathione peroxidase activity. Furthermore, it was revealed that treatment with vitexin induced hypoxia inducible factor 1α subunit (HIF-1α) and vascular endothelial growth factor (VEGF) protein expression, and suppressed phosphorylated-p38 MAP kinase (p38) protein expression in sevoflurane-induced newborn rat. Together, the results of the current study suggest that the protective effect of vitexin reduces sevoflurane-induced neuronal apoptosis through HIF-1α-, VEGF-and p38-associated signaling pathways in newborn rats.

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“…The final concentration of DMSO in the media was less than 0.01 %. Aβ [25][26][27][28][29][30][31][32][33][34][35] was diluted to 1 mM with sterilized saline water and then incubated at 37°C for seven days before use [21]. PC12 cells (1×10 5 cells/well in 96-well plates) were cultured with complete DMEM 24 h for stabilization at 37 °C.…”

Section: Cell Viability Assessment By Mtt Assaymentioning

confidence: 99%

Icariside II, a Phosphodiesterase-5 Inhibitor, Attenuates Beta-Amyloid-Induced Cognitive Deficits via BDNF/TrkB/CREB Signaling

Liu

Gao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Icariside II (ICS II) is an active component from Epimedium brevicornum, a Chinese medicine extensively used in China. Our previous study has proved that ICS II protects against learning and memory impairments and neuronal apoptosis in the hippocampus induced by beta-amyloid_25-35 (Aβ_25-35) in rats. However, its in-depth underlying mechanisms remain still unclear. Hence this study was designed to explore the potential underlying mechanisms of ICS II by experiments with an in vivo model of Aβ_25-35-induced cognitive deficits in rats combined with a neuronal-like PC12 cells injury in vitro model. Methods: The cognitive deficits was measured using Morris water maze test, and apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial ROS levels were detected by TUNEL, DCFH-DA and Mito-SOX staining, respectively. Expression of Bcl-2, Bax, brain derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and cAMP response element binding (p-CREB) and active-Caspase 3 levels were evaluated by Western blot. Results: It was found that ICS II, a phosphodiesterase-5 inhibitor, significantly attenuated cognitive deficits caused by Aβ_25-35 injection in rats, and ICS II not only significantly enhanced the expression of BDNF and TrkB, but also activated CREB. Furthermore, ICS II also significantly abrogated Aβ_25-35-induced PC12 cell injury, and inhibited Aβ_25-35-induced intracellular reactive oxygen species (ROS) overproduction, as well as mitochondrial ROS levels. In addition, ICS II up-regulated the expressions of BDNF and TrkB consistent with the findings in vivo. ANA-12, a TrkB inhibitor, blocked the neuroprotective effect of ICS II on Aβ_25-35-induced neuronal injury. Conclusion: ICS II mitigates Aβ_25-35-induced cognitive deficits and neuronal cell injury by upregulating the BDNF/TrkB/CREB signaling, suggesting that ICS II can be used as a potential therapeutic agent for dementia, such as Alzheimer’s disease.

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Insulin protects against Aβ-induced spatial memory impairment, hippocampal apoptosis and MAPKs signaling disruption

Cited by 64 publications

References 64 publications

The Interplay of Akt and ERK in Aβ Toxicity and Insulin-Mediated Protection in Primary Hippocampal Cell Culture

The Interplay of Akt and ERK in Aβ Toxicity and Insulin-Mediated Protection in Primary Hippocampal Cell Culture

Protective effect of vitexin reduces sevoflurane-induced neuronal apoptosis through HIF-1α, VEGF and p38 MAPK signaling pathway inï¿½vitro and in newborn rats

Icariside II, a Phosphodiesterase-5 Inhibitor, Attenuates Beta-Amyloid-Induced Cognitive Deficits via BDNF/TrkB/CREB Signaling

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