GM1 improves neurofascin155 association with lipid rafts and prevents rat brain myelin injury after hypoxia-ischemia

Abstract

White matter injury characterized by damage to myelin is an important process in hypoxic-ischemic brain damage (HIBD). Because the oligodendrocyte-specific isoform of neurofascin, neurofascin 155 (NF155), and its association with lipid rafts are essential for the establishment and stabilization of the paranodal junction, which is required for tight interaction between myelin and axons, we analyzed the effect of monosialotetrahexosyl ganglioside (GM1) on NF155 expression and its association with lipid rafts after HIBD in Sprague-Dawley rats, weighing 12-15 g, on day 7 post-partum (P7; N = 20 per group). HIBD was induced on P7 and the rats were divided into two groups: one group received an intraperitoneal injection of 50 mg/kg GM1 three times and the other group an injection of saline. There was also a group of 20 sham-operated rats. After sacrifice, the brains of the rats were removed on P30 and studied by immunochemistry, SDS-PAGE, Western blot analysis, and electron microscopy. Staining showed that the saline group had definite rarefaction and fragmentation of brain myelin sheaths, whereas the GM1 group had no obvious structural changes. The GM1 group had 1.9-2.9-fold more GM1 in lipid rafts than the saline group (fraction 3-6; all P < 0.05) and 0.5-2.4-fold higher expression of NF155 in lipid rafts (fraction 3-5; all P < 0.05). Injection of GM1 increased the content of GM1 in lipid rafts as well as NF155 expression and its lipid raft association in HIBD rat brains. GM1 may repair the structure of lipid rafts, promote the association of NF155 (or other important proteins) with lipid rafts, stabilize the structure of paranodes, and eventually prevent myelin sheath damage, suggesting a novel mechanism for its neuroprotective properties.

Gangliosides in the Brain: Physiology, Pathophysiology and Therapeutic Applications

“…GM1 also decreased cerebral edema and cognitive and motor impairment in a rat model of high altitude-induced hypoxia, via activation of the PI3K/AKT-Nrf2 pathway (Gong et al, 2018). Finally, it has been suggested that an additional mechanism of neuroprotection by GM1 in stroke models could be through the restoration/protection of paranodal regions in myelinated axons and prevention of myelin sheath rarefaction (Zhang et al, 2011).…”

The Possible Damaged Mechanism and the Preventive Effect of Monosialotetrahexosylganglioside in a Rat Model of Cerebral Ischemia-Reperfusion Injury

“…GM1 may repair the structure of lipid rafts, promote the association of NF155 (or other important proteins) with lipid rafts, stabilize the structure of paranodes, prevent myelin sheath damage, and eventually act on its neuroprotective properties. 23 Its potential effect mechanisms were to prevent the excessive release and/or reuptake dysfunction of EAAs and the EAAsmediated lipid peroxidation and calcium homeostasis disorder.…”

Ganglioside GM1 for ischemic stroke: An update (2005-2015)

“…The concentration of GM1 has been found to undergo a significant decrease in this process [14]. Exogenous GM1 injection has been shown to reduce the damage of myelin sheaths, the primary characteristic of white matter injury, and eventually prevent brain injury.…”

“…Exogenous GM1 injection has been shown to reduce the damage of myelin sheaths, the primary characteristic of white matter injury, and eventually prevent brain injury. The neuroprotective effect of GM1 might involve promoting the association of neurofascin 155 (or other important proteins) with lipid rafts, increasing the expression of myelin basic protein, and subsequent stabilizing the structure of paranodes [13,14]. In a recent study by Whitehead et al [15], middle cerebral artery occlusion (MCAO) resulted in a transient induction of GM1 at the border of the infarcted tissue in adult mice.…”