Glial Metabolic Rewiring Promotes Axon Regeneration and Functional Recovery in the Central Nervous System

Li, Feng; Sami, Armin; Noristani, Harun N.; Slattery, Kieran; Qiu, Jingyun; Groves, Thomas; Wang, Shuo; Veerasammy, Kelly; Chen, Yuki X.; Morales, Jorge; Haynes, Paula; Sehgal, Amita; He, Ye; Li, Shuxin; Song, Yuanquan

doi:10.1016/j.cmet.2020.08.015

Cited by 78 publications

(57 citation statements)

References 116 publications

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“…A role for shuttling of lactate between glial cells and axons has been proposed in the regeneration of injured axon in both the central (CNS) and peripheral nervous systems (PNS). In the CNS, there is active inhibition of regeneration by the action of myelin associated proteins and release of CSPG by astrocytes forming the glial scar [ 90 ], thus manipulating this inhibitory environment is viewed as being a viable therapeutic manoeuvre to aid regeneration. In a study, both drosophila and mouse models of injury to CNS axons were used.…”

Section: Regenerationmentioning

confidence: 99%

“…Soon after axotomy there was increased expression of MCT1 and MCT4 transporters, which serve to facilitate lactate exit from the Schwann cell. The rapid increase in AMPK activated protein kinase and mTOR complex 1/2 in the aftermath of injury is suggestive that these signalling pathway are associated with the lactate release and uptake by the axons [ 90 ] ( Figure 4 ).…”

Section: Regenerationmentioning

confidence: 99%

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Universal Glia to Neurone Lactate Transfer in the Nervous System: Physiological Functions and Pathological Consequences

2020

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Whilst it is universally accepted that the energy support of the brain is glucose, the form in which the glucose is taken up by neurones is the topic of intense debate. In the last few decades, the concept of lactate shuttling between glial elements and neural elements has emerged in which the glial cells glycolytically metabolise glucose/glycogen to lactate, which is shuttled to the neural elements via the extracellular fluid. The process occurs during periods of compromised glucose availability where glycogen stored in astrocytes provides lactate to the neurones, and is an integral part of the formation of learning and memory where the energy intensive process of learning requires neuronal lactate uptake provided by astrocytes. More recently sleep, myelination and motor end plate integrity have been shown to involve lactate shuttling. The sequential aspect of lactate production in the astrocyte followed by transport to the neurones is vulnerable to interruption and it is reported that such disparate pathological conditions as Alzheimer’s disease, amyotrophic lateral sclerosis, depression and schizophrenia show disrupted lactate signalling between glial cells and neurones.

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Section: Regenerationmentioning

confidence: 99%

Section: Regenerationmentioning

confidence: 99%

Universal Glia to Neurone Lactate Transfer in the Nervous System: Physiological Functions and Pathological Consequences

2020

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“…What is more, does endogenous 2-HG regulate the functions of other immune cell subsets? Recently, L -2HG is demonstrated to promote axon regeneration in the central nervous system ( Li et al, 2020 ). Therefore, 2-HG may also function in other physiological processes.…”

Section: Discussionmentioning

confidence: 99%

The Roles of 2-Hydroxyglutarate

2021

Front. Cell Dev. Biol.

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2-Hydroxyglutarate (2-HG) is structurally similar to α-ketoglutarate (α-KG), which is an intermediate product of the tricarboxylic acid (TCA) cycle; it can be generated by reducing the ketone group of α-KG to a hydroxyl group. The significant role that 2-HG plays has been certified in the pathophysiology of 2-hydroxyglutaric aciduria (2HGA), tumors harboring mutant isocitrate dehydrogenase 1/2 (IDH1/2mt), and in clear cell renal cell carcinoma (ccRCC). It is taken as an oncometabolite, raising much attention on its oncogenic mechanism. In recent years, 2-HG has been verified to accumulate in the context of hypoxia or acidic pH, and there are also researches confirming the vital role that 2-HG plays in the fate decision of immune cells. Therefore, 2-HG not only participates in tumorigenesis. This text will also summarize 2-HG’s identities besides being an oncometabolite and will discuss their enlightenment for future research and clinical treatment.

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“…Over time, varieties of extrinsic factors were discovered to have a relationship with the regeneration process after CNS injury. Glial scars, myelin debris, and axonal growth inhibitors form significant impediments to axonal regeneration ( Li et al, 2020 ). Glial scars, which serve a primary role in preventing inflammatory processes from propagating to healthy tissue ( Cregg et al, 2014 ), also create a physical barrier in which axonal tips get trapped.…”

Section: Introductionmentioning

confidence: 99%

Roles of Non-coding RNAs in Central Nervous System Axon Regeneration

Jia

Tang

et al. 2021

Front. Neurosci.

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Axons in the central nervous system often fail to regenerate after injury due to the limited intrinsic regeneration ability of the central nervous system (CNS) and complex extracellular inhibitory factors. Therefore, it is of vital importance to have a better understanding of potential methods to promote the regeneration capability of injured nerves. Evidence has shown that non-coding RNAs play an essential role in nerve regeneration, especially long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA). In this review, we profile their separate roles in axon regeneration after CNS injuries, such as spinal cord injury (SCI) and optic nerve injury. In addition, we also reveal the interactive networks among non-coding RNAs.

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Glial Metabolic Rewiring Promotes Axon Regeneration and Functional Recovery in the Central Nervous System

Cited by 78 publications

References 116 publications

Universal Glia to Neurone Lactate Transfer in the Nervous System: Physiological Functions and Pathological Consequences

Universal Glia to Neurone Lactate Transfer in the Nervous System: Physiological Functions and Pathological Consequences

The Roles of 2-Hydroxyglutarate

Roles of Non-coding RNAs in Central Nervous System Axon Regeneration

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