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

Ye, Yuqin; Zhao, Zhenyu; Xu, Hao; Zhang, Xin; Su, Xinhong; Yang, Yongxiang; Yu, Xinguang; He, Xiaosheng

doi:10.1155/2016/8072156

Cited by 28 publications

(22 citation statements)

References 42 publications

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“…Fingolimod acts on S1P receptors 1, 3, 4, and 5, while siponimod is more narrowly targeted to S1P receptors 1 and 5. 59 S1PR1 selective agents have shown benefits in animal models of neurodegeneration, 65,66 and S1PR5 is expressed by oligodendrocytes, 67 suggesting that these are the dominant receptors responsible for mediating CNS effects. However, human astrocytes can mediate S1P signaling through either S1PR1 or S1PR3, 68 thus the difference in selectivity for S1PR3 may underlie the differential activity in PMS.…”

Section: S1p Modulators: Fingolimod and Siponimodmentioning

confidence: 99%

Impact of trial design and patient heterogeneity on the identification of clinically effective therapies for progressive MS

et al. 2018

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Clinically effective immunomodulatory therapies have been developed for relapsing-remitting multiple sclerosis (RRMS), but they have generally not translated to a corresponding slowing of disability accumulation in progressive forms of multiple sclerosis (MS). Since disability is multifaceted, progressive patients are heterogeneous, and the drivers of disease progression are still unclear, it has been difficult to identify the most informative outcome measures for progressive trials. Historically, secondary outcome measures have focused on inflammatory measures, which contributed to the recent identification of immunomodulatory therapies benefiting younger patients with more inflammatory progressive MS. Meanwhile, agents capable of treating late-stage disease have remained elusive. Consequently, measures of neurodegeneration are becoming common. Here, we review completed clinical trials testing immunomodulatory therapies in primary progressive multiple sclerosis (PPMS) or secondary progressive multiple sclerosis (SPMS) and discuss the features contributing to trial design variability in relation to trial outcomes, and how efforts toward better patient stratification and inclusion of reliable progression markers could improve outcomes.

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Section: S1p Modulators: Fingolimod and Siponimodmentioning

confidence: 99%

Impact of trial design and patient heterogeneity on the identification of clinically effective therapies for progressive MS

et al. 2018

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“…Neural stem cells, located in the subgranular zone of hippocampal dentate gyrus, are capable of proliferating, differentiating and integrating into the existing neuronal circuits. These self-renewing cells have the potential to replenish neural loss and restore neurological function after stroke (7). Post-traumatic neurogenesis and cognition recovery has been previously observed to be rescued by the activation of mitogen-activated protein kinase (MEK)/ERK (7).…”

Section: Effect Of Willed Movement Training On Neurorehabilitationmentioning

confidence: 99%

“…These self-renewing cells have the potential to replenish neural loss and restore neurological function after stroke (7). Post-traumatic neurogenesis and cognition recovery has been previously observed to be rescued by the activation of mitogen-activated protein kinase (MEK)/ERK (7). Conditional activation of ERK enhances hippocampus neurogenesis in a rat model of traumatic brain injury, improving the olfactory function under normal conditions and after injury, and inhibition of MEK/ERK abolished the neurogenesis improved by sphingosine-1-phosphate receptor 1 activation (7).…”

Section: Effect Of Willed Movement Training On Neurorehabilitationmentioning

confidence: 99%

“…Post-traumatic neurogenesis and cognition recovery has been previously observed to be rescued by the activation of mitogen-activated protein kinase (MEK)/ERK (7). Conditional activation of ERK enhances hippocampus neurogenesis in a rat model of traumatic brain injury, improving the olfactory function under normal conditions and after injury, and inhibition of MEK/ERK abolished the neurogenesis improved by sphingosine-1-phosphate receptor 1 activation (7). The pivotal role of ERK in endogenous neurogenesis is likely mediated through regulating multiple factors, including cyclic adenosine monophosphate response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF), nerve growth factor, and synaptophysin (SYP) (8,9).…”

Section: Effect Of Willed Movement Training On Neurorehabilitationmentioning

confidence: 99%

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Effect of willed movement training on neurorehabilitation after focal cerebral ischemia and on the neural plasticity-associated signaling pathway

et al. 2017

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Neurorehabilitation training is a therapeutic intervention for the loss of neural function induced by focal cerebral ischemia, however, the effect varies depending on the neurorehabilitation exercises. Willed movement (WM) training is defined as task‑oriented training, which increases enthusiasm of patients to accomplish a specific task. The current study was performed to the evaluate effect of WM training on neurorehabilitation following focal cerebral ischemia, and further investigate the influence on neural plasticity‑associated signaling pathway. Sprague‑Dawley rats following temporary middle cerebral artery occlusion (tMCAO) were randomly divided into four groups: tMCAO (no rehabilitation training), CR (control rehabilitation), EM (environmental modification) and WM groups. Rats in the CR group were forced to exercise (running) in a rotating wheel. In the WM group, food was used to entice rats to climb on a herringbone ladder. Herringbone ladders were also put into the cages of the rats in the CR and EM groups, however without the food attraction. WM group exhibited an improvement in neurobehavioral performance compared with other groups. TTC staining indicated an evident reduction in brain damage in the WM group. There were increased synaptic junctions following WM training, based on the observations of transmission election microscopy. Investigation of the molecular mechanism suggested that WM training conferred the greatest effect on stimulating the extracellular signal‑related kinase (ERK)/cyclic adenosine monophosphate response element‑binding protein 1 (CREB) pathway and glutamate receptor 2 (GluR2)/glutamate receptor interacting protein 1‑associated protein 1 (GRASP‑1)/protein interacting with C‑kinase 1 (PICK1) cascades among groups. Collectively, the improvement of neurobehavioral performance by WM training following tMCAO is suggested to involve the ERK/CREB pathway and GluR2/GRASP‑1/PICK1 cascades. The present study provided a preliminary foundation for future research on the therapeutic effect of WM training against stroke‑induced neuron damage.

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“…ERK is the most downstream protein kinase of the canonical Ras-Raf-MEK-ERK cascade that can be suppressed by Raf kinase inhibitory protein, PEBP1 (Pyo et al, 2018). ERK signaling is critical in early neurogenesis (Ye et al, 2016); it directs self-renewal, division and differentiation of neural progenitor cells (Dee et al, 2016;Pillat et al, 2016). ERK signaling is dispensable for morphological and survival of large Ctip2 + neurons in layer 5 (Xing et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Lack of dcf1 leads to neuronal migration delay, axonal swollen and autism-related deficits

Feng

Chen

Sun

et al. 2020

Preprint

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Perturbed neuronal migration and abnormal axonogenesis have been shown to be implicated in the pathogenesis of autism spectrum disorder (ASD). However, the molecular mechanism remains unknown. Here we demonstrate that dendritic cell factor 1(DCF1) is involved in neuronal migration and axonogenesis. The deletion of dcf1 in mice delays the localization of callosal projection neurons, while dcf1 overexpression restores normal migration. Delayed neurons appear as axon swelling and axonal boutons loss, resulting in a permanent deficit in the callosal projections.Western blot analysis indicates that absence of dcf1 leads to the abnormal activation of ERK signal. Differential protein expression assay shows that PEBP1, a negative regulator of the ERK signal, is significant downregulation in dcf1 KO mice. Direct interaction between DCF1 and PEBP1 is confirmed by Co-immunoprecipitation test, thus indicating that DCF1 regulates the ERK signal in a PEBP1-dependent pattern. As a result of the neurodevelopmental migration disorder, dcf1 deletion results in ASD-like behaviors in mice. This finding identifies a link between abnormal activated ERK signaling, delayed neuronal migration and autistic-like behaviors in humans.

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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

Cited by 28 publications

References 42 publications

Impact of trial design and patient heterogeneity on the identification of clinically effective therapies for progressive MS

Impact of trial design and patient heterogeneity on the identification of clinically effective therapies for progressive MS

Effect of willed movement training on neurorehabilitation after focal cerebral ischemia and on the neural plasticity-associated signaling pathway

Lack of dcf1 leads to neuronal migration delay, axonal swollen and autism-related deficits

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