The metabolomic profiling identifies N, N‐dimethylglycine as a facilitator of dorsal root ganglia neuron axon regeneration after injury

Abstract

Identifying novel molecules involved in axon regeneration of neurons in the peripheral nervous system (PNS) will be of benefit in obtaining a therapeutic strategy for repairing axon damage both in the PNS and the central nervous system (CNS). Metabolism and axon regeneration are tightly connected. However, the overall metabolic processes and the landscape of the metabolites in axon regeneration of PNS neurons are uncovered. Here, we used an ultra high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC‐QTOFMS)‐based untargeted metabolomics to analyze dorsal root ganglia (DRG) metabolic characteristics at different time points post sciatic nerve injury and acquired hundreds of differentially changed metabolites. In addition, the results reveal that several metabolic pathways were significantly altered, such as ‘Histidine metabolism’, ‘Glycine serine and threonine metabolism’, ‘Arginine and proline metabolism’, ‘taurine and hypotaurine metabolism’ and so on. Given metabolite could alter a cell's or an organism's phenotype, further investigation demonstrated that N, N‐dimethylglycine (DMG) has a promoting effect on the regenerative ability post injury. Overall, our data may serve as a resource useful for further understanding how metabolites contribute to axon regeneration in DRG during sciatic nerve regeneration and suggest DMG may be a candidate drug to repair nerve injury.

N,N-Dimethylglycine Sodium Salt Exerts Marked Anti-Inflammatory Effects in Various Dermatitis Models and Activates Human Epidermal Keratinocytes by Increasing Proliferation, Migration, and Growth Factor Release

“…Further, by using the classical UVB irradiation-induced model system, we also showed that DMG-Na significantly counteracted the effect of UVB irradiation to upregulate ROS production of epidermal keratinocytes. This corroborates well with previous studies that reported the profound antioxidant and scavenger actions of DMG and its sodium salt in practically all (extra-cutaneous) tissues measured so far [14][15][16][17][18][19][20][21][22][23], including the gastrointestinal tract [14][15][16], liver [17,18], skeletal muscle [19][20][21], and peripheral neurons [22].…”

“…Besides these effects, it has also been proposed that DMG and its sodium salt may function as a source of glycine for glutathione synthesis, and hence may improve cellular and tissue antioxidant capacities. Indeed, in various animal studies that model pathologies of, e.g., the gastrointestinal tract [14][15][16], liver [17,18], skeletal muscle [19][20][21], and peripheral neurons [22], both DMG and its sodium salt were shown to reduce oxidative stress damage by exhibiting scavenger activities against excess free radicals and to improve the utilization of oxygen [14][15][16][17][18][19][20][21][22][23]; hence, they can be conductive to the body's redox status and its regeneration and repair. Moreover, DMG, acting as a methyl donor, has been suggested to improve immunity and enhance immune responses [24][25][26].…”

Investigation of seasonal changes in lipid synthesis and metabolism-related genes in the oviduct of Chinese brown frog (<em>Rana dybowskii</em>)

“…Oviductal samples were prepared with reference to those mentioned in previous publications, with some modifications. 36 , 37 25 mg of oviduct tissue was weighed, and six biological replicates were used for each of the breeding season and pre-brumation. 500 μL extract solution (acetonitrile:methanol:water, 2:2:1) containing isotopically-labelled internal standard (L-2-Chlorophenylalanine) mixture was added.…”

Cellular complexity of the peripheral nervous system: Insights from single-cell resolution

“…However, single-cell multi-omics mainly focus on the CNS, and their application in the PNS is relatively limited. The methylation and metabonomics of DRG have been sequenced at the bulk level ( Weng et al, 2018 ; Zhang et al, 2022 ). Mapping these dates to single-cell transcriptomes may offer enlightenment to discover specific responded cell sub-types under naïve or disease states.…”