In vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity

Wen, Shu-yun; Li, Aimin; Mi, Kuan-qing; Wang, Rui-zheng; Li, Hao; Liu, Hua-xiang; Xing, Yi

doi:10.4103/1673-5374.217352

Cited by 14 publications

(7 citation statements)

References 38 publications

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“…Furthermore, CNTF exerts myotrophic activities and is also classified as a myokine that is capable of modulating osteoblast function (Pasquin et al, 2015 ). Results from a previous study revealed that CNTF protects against glutamate-induced neurotoxicity in dorsal root ganglion neurons via the regulation of the JAK2/STAT3 and PI3K/AKT pathways (Wen et al, 2017 ). However, the expression and potential effects of CNTF signaling on hippocampal neurons have not been studied in CCH.…”

Section: Discussionmentioning

confidence: 99%

Dl-3-n-Butylphthalide Alleviates Hippocampal Neuron Damage in Chronic Cerebral Hypoperfusion via Regulation of the CNTF/CNTFRα/JAK2/STAT3 Signaling Pathways

Wei

Zhu

et al. 2021

Front. Aging Neurosci.

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Chronic cerebral hypoperfusion (CCH) contributes to cognitive impairments, and hippocampal neuronal death is one of the key factors involved in this process. Dl-3-n-butylphthalide (D3NB) is a synthetic compound originally isolated from the seeds of Apium graveolens, which exhibits neuroprotective effects against some neurological diseases. However, the protective mechanisms of D3NB in a CCH model mimicking vascular cognitive impairment remains to be explored. We induced CCH in rats by a bilateral common carotid artery occlusion (BCCAO) operation. Animals were randomly divided into a sham-operated group, CCH 4-week group, CCH 8-week group, and the corresponding D3NB-treatment groups. Cultured primary hippocampal neurons were exposed to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic CCH in vitro. We aimed to explore the effects of D3NB treatment on hippocampal neuronal death after CCH as well as its underlying molecular mechanism. We observed memory impairment and increased hippocampal neuronal apoptosis in the CCH groups, combined with inhibition of CNTF/CNTFRα/JAK2/STAT3 signaling, as compared with that of sham control rats. D3NB significantly attenuated cognitive impairment in CCH rats and decreased hippocampal neuronal apoptosis after BCCAO in vivo or OGD/R in vitro. More importantly, D3NB reversed the inhibition of CNTF/CNTFRα expression and activated the JAK2/STAT3 pathway. Additionally, JAK2/STAT3 pathway inhibitor AG490 counteracted the protective effects of D3NB in vitro. Our results suggest that D3NB could improve cognitive function after CCH and that this neuroprotective effect may be associated with reduced hippocampal neuronal apoptosis via modulation of CNTF/CNTFRα/JAK2/STAT3 signaling pathways. D3NB may be a promising therapeutic strategy for vascular cognitive impairment induced by CCH.

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Section: Discussionmentioning

confidence: 99%

Dl-3-n-Butylphthalide Alleviates Hippocampal Neuron Damage in Chronic Cerebral Hypoperfusion via Regulation of the CNTF/CNTFRα/JAK2/STAT3 Signaling Pathways

Wei

Zhu

et al. 2021

Front. Aging Neurosci.

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“…Both these principles might apply to CNTF and GDNF. These two neurotrophic factors are partially redundant as they are both known to activate the PI3K/Akt pathway in target cells downstream of their receptors thus enhancing neuronal survival, neurite growth and sprouting [2,13,14,20]. On the other hand, the two pathways also involve mutually non-redundant intercellular signaling axes, as CNTF also operates though the JAK2/STAT3 pathway [13,14], while GNDF activates the Ras/…”

Section: Discussionmentioning

confidence: 99%

“…These two neurotrophic factors are partially redundant as they are both known to activate the PI3K/Akt pathway in target cells downstream of their receptors thus enhancing neuronal survival, neurite growth and sprouting [ 2 , 13 , 14 , 20 ]. On the other hand, the two pathways also involve mutually non-redundant intercellular signaling axes, as CNTF also operates though the JAK2/STAT3 pathway [ 13 , 14 ], while GNDF activates the Ras/MAP kinase pathway [ 2 , 13 , 20 ]. The synergistic effect of the CNTF/GNDF combination on the directed neurite growth does not significantly change within a 10-fold range of the neurotrophic factor mix, suggesting saturation of this response at lower concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…In the nervous system, it functions to support the survival and differentiation of neurons and glia, as well as neurite outgrowth. At the intracellular level, it activates the PI3K/Akt and JAK2/STAT3 pathways [11][12][13][14]. Unlike many other neurotrophic factors, CNTF is abundantly expressed in the uninjured peripheral nerves, but is suppressed during neural regeneration.…”

Section: Introductionmentioning

confidence: 99%

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Synergistic effect of CNTF and GDNF on directed neurite growth in chick embryo dorsal root ganglia

et al. 2020

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It is often critical to improve the limited regenerative capacity of the peripheral nerves and direct neural growth towards specific targets, such as surgically implanted bioengineered constructs. One approach to accomplish this goal is to use extrinsic neurotrophic factors. The candidate factors first need to be identified and characterized in in vitro tests for their ability to direct the neurite growth. Here, we present a simple guidance assay that allows to assess the chemotactic effect of signaling molecules on the growth of neuronal processes from dorsal root ganglia (DRG) using only standard tissue culture materials. We used this technique to quantitatively determine the combined and individual effects of the ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF) on neurite outgrowth. We demonstrated that these two neurotrophic factors, when applied in a 1:1 combination, but not individually, induced directed growth of neuronal processes towards the source of the gradient. This chemotactic effect persists without significant changes over a wide (10-fold) concentration range. Moreover, we demonstrated that other, more general growth parameters that do not evaluate growth in a specific direction (such as, neurite length and trajectory) were differentially affected by the concentration of the CNTF/GNDF mixture. Furthermore, GDNF, when applied individually, did not have any chemotactic effect, but caused significant neurite elongation and an increase in the number of neurites per ganglion.

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“…Excitotoxicity caused by glutamate is one of the most frequently studied pathological mechanisms of central nervous system diseases. 20 21 22 The process by which excess quantities of the excitatory neurotransmitter, glutamate, activates N-methyl-D-aspartate receptors (NMDARs) is a key step in the production of excitotoxicity. 23 24 25 After stroke, ischemia and hypoxia cause ion disorder in the neural cells, subsequently leading to cell depolarization and release of excitatory glutamate into the synaptic space.…”

Section: P Athological M Echanisms Of mentioning

confidence: 99%

The role of medical gas in stroke: an updated review

et al. 2019

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In vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity

Cited by 14 publications

References 38 publications

Dl-3-n-Butylphthalide Alleviates Hippocampal Neuron Damage in Chronic Cerebral Hypoperfusion via Regulation of the CNTF/CNTFRα/JAK2/STAT3 Signaling Pathways

Dl-3-n-Butylphthalide Alleviates Hippocampal Neuron Damage in Chronic Cerebral Hypoperfusion via Regulation of the CNTF/CNTFRα/JAK2/STAT3 Signaling Pathways

Synergistic effect of CNTF and GDNF on directed neurite growth in chick embryo dorsal root ganglia

The role of medical gas in stroke: an updated review

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