Roflumilast ameliorates cognitive impairment in APP/PS1 mice via cAMP/CREB/BDNF signaling and anti-neuroinflammatory effects

Feng, Huancun; Wang, Canmao; He, Wei; Wu, Xin; Li, Shujie; Zeng, Zhenkun; Wei, Mei-Dan; He, Binghong

doi:10.1007/s11011-018-0374-4

Cited by 51 publications

(23 citation statements)

References 52 publications

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“…Reduced adenosine monophosphate levels have significant consequences, such as impairments in cellular energy homeostasis, because adenosine monophosphate plays a central role in glucose and lipid metabolism through the adenosine monophosphate-activated protein kinase, which is known to be decreased in AD brains [39,40]. In addition, significantly decreased adenosine monophosphate levels were detected in the hippocampus and cortex of APP/PS1 mice [13].…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide attenuates the decrease in dendritic spine density in hippocampal primary neurons from 5xFAD mice, an Alzheimer’s disease animal model

Kim

Cho

2020

Mol Brain

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Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by memory loss and the presence of amyloid plaques and neurofibrillary tangles in the patients' brains. In this study, we investigated the alterations in metabolite profiles of the hippocampal tissues from 6, 8, and 12 month-old wild-type (WT) and 5xfamiliar AD (5xFAD) mice, an AD mouse model harboring 5 early-onset familiar AD mutations, which shows memory loss from approximately 5 months of age, by exploiting the untargeted metabolomics profiling. We found that nicotinamide and adenosine monophosphate levels have been significantly decreased while lysophosphatidylcholine (LysoPC) (16:0), LysoPC (18:0), and lysophosphatidylethanolamine (LysoPE) (16:0) levels have been significantly increased in the hippocampi from 5xFAD mice at 8 months or 12 months of age, compared to those from age-matched wild-type mice. In the present study, we focused on the role of nicotinamide and examined if replenishment of nicotinamide exerts attenuating effects on the reduction in dendritic spine density in hippocampal primary neurons from 5xFAD mice. Treatment with nicotinamide attenuated the deficits in spine density in the hippocampal primary neurons derived from 5xFAD mice, indicating a potential role of nicotinamide in the pathogenesis of AD. Taken together, these findings suggest that the decreased hippocampal nicotinamide level could be linked with AD pathogenesis and be a useful therapeutic target for AD.

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Section: Discussionmentioning

confidence: 99%

Nicotinamide attenuates the decrease in dendritic spine density in hippocampal primary neurons from 5xFAD mice, an Alzheimer’s disease animal model

Kim

Cho

2020

Mol Brain

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“…BDNF, a neurotrophin playing essential roles in neurogenesis, is related to neuronal excitability, synaptic transmission, and maintenance of neuronal plasticity 58,59 . In addition, it has been documented that BDNF attenuates TNF-α and IL-1β by inhibiting NF-κB signalling 60 .…”

Section: Discussionmentioning

confidence: 99%

Inulin ameliorates schizophrenia via modulation of the gut microbiota and anti-inflammation in mice

et al. 2021

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“…Fisetin is present in human diet and has benefit to nervous system. In recent years, human clinical trial with fisetin has been performed for brain ischemic stroke with encouraging outcomes (Feng et al, 2019). There is no evidence for either short-or long-term toxicity of fisetin (Currais et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…The activation of CREB pathway is closely correlated with the number of surviving neurons, which play important roles in learning and memory in brain (Caracciolo et al, 2018). CREB can also regulate various targeting molecular, including the BDNF, which is essential for neuronal development and survival, synaptic plasticity, and cognitive function (Feng et al, 2019). In neuronal cells, the activation of CREB can be stimulated by the phosphorylation of the upstream PI3K and its effector Akt.…”

Section: Introductionmentioning

confidence: 99%

Fisetin Prevents HT22 Cells From High Glucose-Induced Neurotoxicity via PI3K/Akt/CREB Signaling Pathway

et al. 2020

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Hyperglycemia has been widely considered as a key risk factor for diabetic encephalopathy which can cause neuronal apoptosis and cognitive deficits. The flavonoid compound, fisetin, possesses potential neuroprotective effects and also enhances learning and memory. However, the role of fisetin in hyperglycemia-induced neuronal cytotoxicity has not been fully elucidated. In the present study, HT22 murine hippocampal neuronal cell line was used to establish the injured cell model. Cell proliferation and cytotoxicity assay, Hoechst 33258 staining, qRT-PCR, western blot analysis, and specific inhibitor were used to investigate the effect and molecular mechanisms of fisetin on high glucose (HG)-induced neurotoxicity in HT22 cells. Our results showed that 125 µM and 48 h of treatment was identified as optimal damage parameter of HG. Fisetin significantly improved HG-inhibited cell viability. The levels of LDH, malondialdehyde (MDA), and superoxide dismutase (SOD) were noticeably modulated by fisetin, which alleviated HG-induced HT22 cell oxidative damage. Besides, the apoptosis of HT22 cells was rescued by fisetin pretreatment. In addition, fisetin also prevented HG-induced downregulation of the mRNA expression of Bdnf, Gdnf, synaptophysin (Syp), and glutamate ionotropic receptor AMPA type subunit 1 (Gria1) in cells. More importantly, the decreased phosphorylation of phosphoinositide 3 kinase (PI3K), Akt, and cAMP-response element binding protein (CREB) was rescued by fisetin treatment and that neuroprotective effect of fisetin was partially blocked by PI3K inhibitor, LY294002. These findings indicate that fisetin has potent neuroprotective effect and prevents HG-induced neurotoxicity by activation of PI3K/Akt/CREB pathway.

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Roflumilast ameliorates cognitive impairment in APP/PS1 mice via cAMP/CREB/BDNF signaling and anti-neuroinflammatory effects

Cited by 51 publications

References 52 publications

Nicotinamide attenuates the decrease in dendritic spine density in hippocampal primary neurons from 5xFAD mice, an Alzheimer’s disease animal model

Nicotinamide attenuates the decrease in dendritic spine density in hippocampal primary neurons from 5xFAD mice, an Alzheimer’s disease animal model

Inulin ameliorates schizophrenia via modulation of the gut microbiota and anti-inflammation in mice

Fisetin Prevents HT22 Cells From High Glucose-Induced Neurotoxicity via PI3K/Akt/CREB Signaling Pathway

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