Netrin-1 rescues neuron loss by attenuating secondary apoptosis in ipsilateral thalamic nucleus following focal cerebral infarction in hypertensive rats

Liao, Songjie; Gong, Qiong; Chen, X.-R.; Ye, L.-X.; Ding, Qiao; Zeng, Jinsheng; Yu, Jing

doi:10.1016/j.neuroscience.2012.11.059

Cited by 31 publications

(28 citation statements)

References 38 publications

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“…With regard to apoptosis, previous studies demonstrated that deletion of NTN-1 significantly contributed to substantial neuronal apoptosis and cell death in NTN-1 knockout mice during brainstem development (Llambi et al, 2001). In contrast, NTN-1 treatment prevented ischemia-induced apoptosis in the brain, heart and kidney via different signaling pathways (Layne et al, 2015; Liao et al, 2013; Wang et al, 2009; Wu et al, 2008). In the present study, we observed that the expression of endogenous NTN-1 was upregulated as early as 12h post SAH.…”

Section: Discussionmentioning

confidence: 90%

“…Moreover, it is now well established that NTN-1 exerts versatile functions in diverse biological processes, such as cell survival, differentiation, apoptosis, angiogenesis and tissue morphogenesis (Lai Wing Sun et al, 2011; Lu et al, 2012; Mehlen and Furne, 2005; Wilson et al, 2006). Specifically, NTN-1 has been regarded as an anti-apoptotic molecule in various tissues, including brain, heart, kidney, and cancer (Layne et al, 2015; Liao et al, 2013; Llambi et al, 2001; Mehlen and Guenebeaud, 2010; Wang et al, 2009; Wu et al, 2008). In the adult brain, previous studies showed that NTN-1 could attenuate ischemia-induced neuronal apoptosis and reduce infarct size, as well as improve neurological function after ischemic stroke (Liao et al, 2013; Wu et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, NTN-1 has been regarded as an anti-apoptotic molecule in various tissues, including brain, heart, kidney, and cancer (Layne et al, 2015; Liao et al, 2013; Llambi et al, 2001; Mehlen and Guenebeaud, 2010; Wang et al, 2009; Wu et al, 2008). In the adult brain, previous studies showed that NTN-1 could attenuate ischemia-induced neuronal apoptosis and reduce infarct size, as well as improve neurological function after ischemic stroke (Liao et al, 2013; Wu et al, 2008). However, the anti-apoptotic property of NTN-1 by interacting with deleted in colorectal cancer (DCC) receptor has not been reported in the setting of SAH.…”

Section: Introductionmentioning

confidence: 99%

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Intranasal administration of recombinant Netrin-1 attenuates neuronal apoptosis by activating DCC/APPL-1/AKT signaling pathway after subarachnoid hemorrhage in rats

et al. 2017

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Neuronal apoptosis is a crucial pathological process in early brain injury after subarachnoid hemorrhage (SAH). The effective therapeutic strategies to ameliorate neuronal apoptosis are still absent. We intended to determine whether intranasal administration of exogenous Netrin-1 (NTN-1) could attenuate neuronal apoptosis after experimental SAH, specifically via activating DCC-dependent APPL-1/AKT signaling cascade. Two hundred twenty-five male Sprague-Dawley rats were subjected to the endovascular perforation model of SAH. Recombinant human NTN-1 (rNTN-1) was administered intranasally. NTN-1 small interfering RNA (siRNA), APPL-1 siRNA, and AKT inhibitor MK2206 were administered through intracerebroventricular (i.c.v.) injection. SAH grade, neurological score, neuronal apoptosis assessed by cleaved caspase-3 (CC-3) expression and Fluoro-Jade C (FJC) staining, double immunofluorescence staining, and Western blot were examined. Our results revealed that endogenous NTN-1 level was increased after SAH. Administration of rNTN-1 improved neurological outcomes at 24 h and 72 h after SAH, while knockdown of endogenous NTN-1 worsened neurological impairments. Furthermore, exogenous rNTN-1 treatment promoted APPL-1 activation, increased phosphorylated-AKT and Bcl-2 expression, as well as decreased apoptotic marker CC-3 expression and the number of FJC-positive neurons, thereby alleviated neuronal apoptosis. Conversely, APPL-1 siRNA and MK2206 abolished the anti-apoptotic effect of exogenous rNTN-1 at 24 h after SAH. Collectively, intranasal administration of exogenous rNTN-1 attenuated neuronal apoptosis and improved neurological function in SAH rats, at least in apart via activating DCC/APPL-1/AKT signaling pathway.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intranasal administration of recombinant Netrin-1 attenuates neuronal apoptosis by activating DCC/APPL-1/AKT signaling pathway after subarachnoid hemorrhage in rats

et al. 2017

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“…This process may depend on the UNC5H2 receptor. Insufficient expression of endogenous netrin-1 may cause secondary damage in the VPN after ischemic stroke [16] .…”

Section: Ischemiamentioning

confidence: 99%

“…In addition to its involvement in guiding axon migration during embryonic development, netrin-1 functions in organ formation [3][4][5][6] , tumorigenesis [7] , inflammation [8,9] , and anti-apoptotis [10] , as well as being a potential biomarker for renal injury and certain cancers [11,12] . It also promotes the recovery of neuronal function after cerebral ischemia in animal models [13][14][15][16] . Importantly, a growing number of studies have focused on elucidating the effects of netrin-1 on angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Axon guidance factor netrin-1 and its receptors regulate angiogenesis after cerebral ischemia

Ding

Liao

2014

Neurosci. Bull.

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Neurogenesis and angiogenesis play important roles in functional recovery after ischemic stroke. When cerebral ischemia occurs, axon regeneration can compensate for the loss of apoptotic neurons in the ischemic area. The formation of new blood vessels ameliorates the local decrease in blood supply, enhancing the supply of oxygen and nutrients to newly-formed neurons. New blood vessels also act as a scaffold for the migration of neuroblasts to the infarct area after ischemic stroke. In light of this, researchers have been actively searching for methods to treat cerebral infarction. Netrins were fi rst identifi ed as a family of proteins that mediate axon guidance and direct axon migration during embryogenesis. Later studies have revealed other functions of this protein family. In this review, we focus on netrin-1, which has been shown to be involved in axon migration and angiogenesis, which are required for recovery after cerebral ischemia. Thus, therapies targeting netrin-1 may be useful for the treatment of ischemic stroke.

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Netrin‐1 overexpression improves neurobehavioral outcomes and reduces infarct size via inhibition of the notch1 pathway following experimental stroke

Yang

et al. 2017

J of Neuroscience Research

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Stroke is a leading cause of morbidity and mortality worldwide. Administration of Netrin-1 during the peri-infarct period has been shown to decrease infarct size in rats; however, the underlying mechanism is unclear. We addressed this question in the present study by inducing stroke in rats via middle cerebral artery occlusion (MCAO), and evaluating the effects of Netrin-1 treatment by neurobehavioral testing, immunocytochemistry, and western blotting. Netrin-1 overexpression increased neurobehavioral test scores and reduced cerebral infarct volume following MCAO via inhibition of the Notch1 signaling pathway. These results demonstrate that early administration of Netrin-1 can is an effective therapeutic approach for improving outcome after stroke. © 2017 Wiley Periodicals, Inc.

show abstract

Netrin-1 rescues neuron loss by attenuating secondary apoptosis in ipsilateral thalamic nucleus following focal cerebral infarction in hypertensive rats

Cited by 31 publications

References 38 publications

Intranasal administration of recombinant Netrin-1 attenuates neuronal apoptosis by activating DCC/APPL-1/AKT signaling pathway after subarachnoid hemorrhage in rats

Intranasal administration of recombinant Netrin-1 attenuates neuronal apoptosis by activating DCC/APPL-1/AKT signaling pathway after subarachnoid hemorrhage in rats

Axon guidance factor netrin-1 and its receptors regulate angiogenesis after cerebral ischemia

Netrin‐1 overexpression improves neurobehavioral outcomes and reduces infarct size via inhibition of the notch1 pathway following experimental stroke

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