Neuronal activity-dependent myelin repair promotes motor function recovery after contusion spinal cord injury

Luo, Meiling; Yin, Ying; Li, Duanfang; Tang, Weiwei; Liu, Yuan; Pan, Lu; Yu, Lehua; Tan, Botao

doi:10.1016/j.brainresbull.2020.11.009

Cited by 13 publications

(9 citation statements)

References 36 publications

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“…To address this question, we employed the adeno-associated virus 8 (AAV8) expressing the Gi-coupled Designer Receptor Exclusively Activated by Designer Drugs (DREADD) hM4Di under the control of the human synapsin promoter to target expression to neurons (AAV-hSn-hM4D(Gi)-mCherry). We injected AAV-hSyn-hM4D(Gi)-mCherry bilaterally in the ACC and after two weeks to allow for viral expression, we administered its DREADD ligand compound 21 (C21) intraperitoneally (IP) one hour before IA training to transiently silence neuronal activity in the ACC (Jendryka et al, 2019; Tran et al, 2020; Luo et al, 2021). In addition to hM4Di, the AAV-hSyn-hM4D(Gi)-mCherry viral construct expresses the fluorescent protein mCherry in neurons.…”

Section: Resultsmentioning

confidence: 99%

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Oligodendrocyte lineage cells driven by neuronal activity in selected brain regions are required for episodic memory formation

Barboza

Bessières

Nazarzoda

et al. 2021

Preprint

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The formation of long-term episodic memories requires the activation of molecular mechanisms in several regions of the medial temporal lobe, including the hippocampus and anterior cingulate cortex (ACC). The extent to which these regions engage distinct mechanisms and cell types to support memory formation is not well understood. Recent studies reported that oligodendrogenesis is essential for learning and long-term memory; however, whether these mechanisms are required only in selected brain regions is still unclear. Also still unknown are the temporal kinetics of engagement of learning-induced oligodendrogenesis and whether this oligodendrogenesis occurs in response to neuronal activity. Here we show that in rats and mice, episodic learning rapidly increases the oligodendrogenesis and myelin biogenesis transcripts olig2, myrf, mbp, and plp1, as well as oligodendrogenesis, in the ACC but not in the dorsal hippocampus (dHC). Region-specific knockdown and knockout of Myrf, a master regulator of oligodendrocyte maturation, revealed that oligodendrogenesis is required for memory formation in the ACC but not the dHC. Chemogenetic neuronal silencing in the ACC showed that neuronal activity is critical for learning-induced oligodendrogenesis. Hence, an activity-dependent increase in oligodendrogenesis in selected brain regions, specifically in the ACC but not dHC, is critical for the formation of episodic memories.

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Section: Resultsmentioning

confidence: 99%

“…one hour before IA training to transiently silence neuronal activity in the ACC (Fig. 7A) (Jendryka et al, 2019;Luo et al, 2021;Tran et al, 2020). In addition to hM4Di, the AAV-hSyn-hM4D(Gi)-mCherry viral construct expresses the fluorescent protein mCherry in neurons.…”

Section: Dreadd-mediated Neuronal Inhibition Impairs Learning-induced...mentioning

confidence: 99%

Oligodendrocyte lineage cells driven by neuronal activity in selected brain regions are required for episodic memory formation

Barboza

Bessières

Nazarzoda

et al. 2021

Preprint

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“…White matter is involved in motor function, and white matter injury is considered to be one of the main pathological changes of multiple nervous system injuries ( Bacmeister et al, 2020 ). Moreover, with the continuous in-depth study of white matter in complex brain functions such as learning, memory and emotion, reducing white matter injury become a potential target to further promote the functional recovery after nervous system damage ( Xin et al, 2020 ; Go et al, 2021 ; Luo et al, 2021 ). Although a previous study has reported that 6-Gingerol can alleviate demyelination induced by multiple sclerosis, the specific mechanism of the oligodendrocytes involved in myelin injury has not been explored ( Han et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

6-Gingerol Alleviates Neonatal Hypoxic-Ischemic Cerebral and White Matter Injury and Contributes to Functional Recovery

Zhao

Yao

et al. 2021

Front. Pharmacol.

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Hypoxic-ischemic encephalopathy (HIE) is one main cause of neonatal death and disability, causing substantial injury to white and gray matter, which can lead to severe neurobehavioral dysfunction, including intellectual disability and dyskinesia. Inflammation, nerve cell death, and white matter injury are important factors in the pathological process of HIE. 6-Gingerol is a ginger extract, which reduces inflammatory response and cell death. However, the role of 6-Gingerol in neonatal hypoxic-ischemic brain injury (HIBI) remains unknown. In this study, we constructed a mouse HIBI model and analyzed the protective effect of 6-Gingerol on HIBI by using behavioral tests, histological staining, qPCR and western blot. Here, we found that 6-Gingerol treatment could alleviate HIBI and improve short-term reflex performance, which is closely related to cell death and neuroinflammation. Additionally, 6-Gingerol reduced neuronal apoptosis, pro-inflammatory factor release, as well as microglial activation. Furthermore, 6-Gingerol significantly improved motor disability, which is associated with white matter damage. Thus, our results showed that 6-Gingerol could reduce the loss of myelin sheaths, alleviate cell death of oligodendrocytes, and stimulate the maturation of oligodendrocytes. In terms of mechanism, we found that 6-Gingerol decreased histone H3K27me3 levels, activated AKT pathway and inhibited the activation of ERK and NF-κB pathway at 3 days post-HIBI. Taken together, our data clearly indicate that 6-Gingerol plays a neuroprotective role against HIBI by epigenetic modification and regulation of AKT, ERK, and NF-κB pathways, inhibiting inflammatory responses and reducing cell death.

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“… 48 Axonal activity has also been shown to influence myelin repair within the injured spinal cord, whereby stimulation of the dorsal CST enhances CST remyelination following SCI, whereas inhibition of this circuit reduced myelination. 49 As such, targeted activation of particular circuits induces adaptive changes that may be favorable when combined with NSPC transplantation. Notably, selective activation of particular circuits during a specific rehabilitation paradigm may induce the mobilized circuits to undergo sprouting and growth into the graft, ultimately leading to synaptogenesis and graft-host interactions.…”

Section: Task-specific Rehabilitationmentioning

confidence: 99%

Incorporating Combinatorial Approaches to Encourage Targeted Neural Stem/Progenitor Cell Integration Following Transplantation in Spinal Cord Injury

Pieczonka

Fehlings

2023

Stem Cells Translational Medicine

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Spinal cord injury (SCI) severely diminishes quality of life and presents patients with a substantial financial burden. The lack of a curative treatment has guided efforts toward identifying potential regenerative treatments. Neural stem/progenitor cell (NSPC) transplantation represents a promising strategy for the regeneration of the injured spinal cord due to the ability of these cells to replace neural cells lost post-injury. However, the transplant-derived oligodendrocytes and neurons need to be able to associate and integrate within the appropriate endogenous circuits to guarantee optimal functional recovery. To date, the integration of these transplant-derived cells has lacked specificity and remains a challenge. As such, it appears that the transplanted cells will require additional guidance cues to instruct the cells where to integrate. In the present review, we propose a variety of combinatorial techniques that can be used in conjunction with NSPC transplantation to direct the cells toward particular circuits of interest. We begin by introducing distinct molecular signatures that assist in the formation of specific circuits during development, and highlight how favorable molecular cues can be incorporated within the cells and their environment to guide the grafted cells. We also introduce alternative methods including task-specific rehabilitation, galvanotaxis, and magnet-based tools, which can be applied to direct the integration of the grafted cells toward the stimulated circuits. Future research examining these combinatorial efforts may serve to improve outcomes following SCI.

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Neuronal activity-dependent myelin repair promotes motor function recovery after contusion spinal cord injury

Cited by 13 publications

References 36 publications

Oligodendrocyte lineage cells driven by neuronal activity in selected brain regions are required for episodic memory formation

Oligodendrocyte lineage cells driven by neuronal activity in selected brain regions are required for episodic memory formation

6-Gingerol Alleviates Neonatal Hypoxic-Ischemic Cerebral and White Matter Injury and Contributes to Functional Recovery

Incorporating Combinatorial Approaches to Encourage Targeted Neural Stem/Progenitor Cell Integration Following Transplantation in Spinal Cord Injury

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