Electrical stimulation at nanoscale topography boosts neural stem cell neurogenesis through the enhancement of autophagy signaling

He, Liumin; Sun, Zhen; Li, Jianshuang; Zhu, Rong; Niu, Ben; Tam, Ka Long; Xiao, Qiao; Jun, Li; Wang, Wenjun; Tsui, Chi Ying; Lee, Vincent Wing Hong; So, Kwok-Fai; Xu, Ying; Ramakrishna, Seeram; Zhou, Qinghua; Chiu, Kin

doi:10.1016/j.biomaterials.2020.120585

Cited by 45 publications

(19 citation statements)

References 58 publications

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“…Our results showed that higher autophagy levels were maintained in the young gerbils after I/R. Recent studies have shown that nanoscale electrical stimulation enhances autophagic signaling, promotes the differentiation of NSCs to mature neurons, and prevents neurodegeneration [ 74 ]. Therefore, our present study showed that promoted cell proliferation, neuroblast differentiation, and neural regeneration in the DG region after I/R were concerned to maintaining autophagy levels.…”

Section: Discussionsupporting

confidence: 52%

Targeting the Erk1/2 and autophagy signaling easily improved the neurobalst differentiation and cognitive function after young transient forebrain ischemia compared to old gerbils

et al. 2022

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The hippocampal neurogenesis occurs constitutively throughout adulthood in mammalian species, but declines with age. In this study, we overtly found that the neuroblast proliferation and differentiation in the subgranular zone and the maturation into fully functional and integrated neurons in the granule-cell layer in young gerbils following cerebral ischemia/reperfusion was much more than those in old gerbils. The neurological function and cognitive and memory-function rehabilitation in the young gerbils improved faster than those in the old one. These results demonstrated that, during long term after cerebral ischemia/reperfusion, the ability of neurogenesis and recovery of nerve function in young animals were significantly higher than that in the old animals. We found that, after 14- and 28-day cerebral ischemia/reperfusion, the phosphorylation of MEK1/2, ERK1/2, p90RSK, and MSK1/2 protein levels in the hippocampus of young gerbils was significantly much higher than that of old gerbils. The levels of autophagy-related proteins, including Beclin-1, Atg3, Atg5, and LC3 in the hippocampus were effectively maintained and elevated at 28 days after cerebral ischemia/reperfusion in the young gerbils compared with those in the old gerbils. These results indicated that an increase or maintenance of the phosphorylation of ERK1/2 signal pathway and autophagy-related proteins was closely associated with the neuroblast proliferation and differentiation and the process of maturation into neurons. Further, we proved that neuroblast proliferation and differentiation in the dentate gyrus and cognitive function were significantly reversed in young cerebral ischemic gerbils by administering the ERK inhibitor (U0126) and autophagy inhibitor (3MA). In brief, following experimental young ischemic stroke, the long-term promotion of the neurogenesis in the young gerbil’s hippocampal dentate gyrus by upregulating the phosphorylation of ERK signaling pathway and maintaining autophagy-related protein levels, it overtly improved the neurological function and cognitive and memory function.

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Section: Discussionsupporting

confidence: 52%

Targeting the Erk1/2 and autophagy signaling easily improved the neurobalst differentiation and cognitive function after young transient forebrain ischemia compared to old gerbils

et al. 2022

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“…[33] In recent years, many CNT-based conductive materials have been implemented to promote neural regeneration and electrophysiological maturation. [34][35][36] Conductive substrate interactions with the membranes of neurons can affect individual neuron activity [37] and promote neural network connectivity and synapse maturation. [38,39] To verify the conductivity of the materials, a semiconductor parameter analyzer was used to measure the electrical conductivity of M. Menelaus wings, SA-CNTs, and CNT/GelMA-integrated wings.…”

Section: Resultsmentioning

confidence: 99%

Topographically Conductive Butterfly Wing Substrates for Directed Spiral Ganglion Neuron Growth

Cao

et al. 2021

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their advantages in functional integration, biomedical engineering materials have been used to facilitate nerve regeneration and to regulate neural behaviors through the use of nerve guidance conduits, [3][4][5] bioactive molecule patterning, [6][7][8][9][10] conductive elements, [11][12][13] and so on. Among these, topographical conductive surfaces have the potential to induce neuron orientation, and functional materials possessing such surfaces have aroused extensive attention. [14,15] As one such material, superaligned carbon-nanotube sheets (SA-CNTs) have excellent electrical conductivity and mechanical properties and thus have been employed in neurobiological studies such as electrophysiological maturation, [16] growth behavior regulation, and nerve regeneration. [17] However, despite the progress made in the application of SA-CNTs, these materials only influence the cultured cells by their aligned direction, and this may limit their efficiency in inducing oriented cell growth due to the difference between the nanometer scale of SA-CNTs and the micrometer scale of cells. In addition, because of the lack of 3D topological structures, these SA-CNTs make it difficult to simulate the extracellular matrix in neural tissues. Therefore, topographical conductive materials with 3D structures and cellular orientation capabilities are still sought. Spiral ganglion neuron (SGN) degeneration canlead to severe hearing loss, and the directional regeneration of SGNs has shown great potential for improving the efficacy of auditory therapy. Here, a novel 3D conductive microstructure with surface topologies is presented by integrating superaligned carbon-nanotube sheets (SA-CNTs) onto Morpho Menelaus butterfly wings for SGN culture. The parallel groove-like topological structures of M. Menelaus wings induce the cultured cells to grow along the direction of its ridges. The excellent conductivity of SA-CNTs significantly improves the efficiency of cellular information conduction. When integrating the SA-CNTs with M. Menelaus wings, the SA-CNTs are aligned in parallel with the M. Menelaus ridges, which further strengthens the consistency of the surface topography in the composite substrate. The SA-CNTs integrated onto butterfly wings provide powerful physical signals and regulate the behavior of SGNs, including cell survival, adhesion, neurite outgrowth, and synapse formation. These features indicate the possibility of directed regeneration after auditory nerve injury.

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“…Basal autophagy is primarily required for adequate neuronal differentiation during development [ 80 ]. Studies have shown that nanoscale electrical stimulation promotes the neurogenesis of neural stem cells by enhancing autophagy signaling [ 81 ]. Our previous research also showed that the promoted cell proliferation, neuroblast differentiation, and neural regeneration after ischemic stroke were concerned with maintaining the autophagy levels [ 82 ].…”

Section: Discussionmentioning

confidence: 99%

Fe3O4 Nanozymes Improve Neuroblast Differentiation and Blood-Brain Barrier Integrity of the Hippocampal Dentate Gyrus in D-Galactose-Induced Aged Mice

Xia

Gao

Peng

et al. 2022

IJMS

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Aging is a process associated with blood–brain barrier (BBB) damage and the reduction in neurogenesis, and is the greatest known risk factor for neurodegenerative disorders. However, the effects of Fe3O4 nanozymes on neurogenesis have rarely been studied. This study examined the effects of Fe3O4 nanozymes on neuronal differentiation in the dentate gyrus (DG) and BBB integrity of D-galactose-induced aged mice. Long-term treatment with Fe3O4 nanozymes (10 μg/mL diluted in ddH2O daily) markedly increased the doublecortin (DCX) immunoreactivity and decreased BBB injury induced by D-galactose treatment. In addition, the decreases in the levels of antioxidant proteins including superoxide dismutase (SOD) and catalase as well as autophagy-related proteins such as Becin-1, LC3II/I, and Atg7 induced by D-galactose treatment were significantly ameliorated by Fe3O4 nanozymes in the DG of the mouse hippocampus. Furthermore, Fe3O4 nanozyme treatment showed an inhibitory effect against apoptosis in the hippocampus. In conclusion, Fe3O4 nanozymes can relieve neuroblast damage and promote neuroblast differentiation in the hippocampal DG by regulating oxidative stress, apoptosis, and autophagy.

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Electrical stimulation at nanoscale topography boosts neural stem cell neurogenesis through the enhancement of autophagy signaling

Cited by 45 publications

References 58 publications

Targeting the Erk1/2 and autophagy signaling easily improved the neurobalst differentiation and cognitive function after young transient forebrain ischemia compared to old gerbils

Targeting the Erk1/2 and autophagy signaling easily improved the neurobalst differentiation and cognitive function after young transient forebrain ischemia compared to old gerbils

Topographically Conductive Butterfly Wing Substrates for Directed Spiral Ganglion Neuron Growth

Fe3O4 Nanozymes Improve Neuroblast Differentiation and Blood-Brain Barrier Integrity of the Hippocampal Dentate Gyrus in D-Galactose-Induced Aged Mice

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