Resveratrol Promotes Nerve Regeneration via Activation of p300 Acetyltransferase-Mediated VEGF Signaling in a Rat Model of Sciatic Nerve Crush Injury

Abstract

Peripheral nerve injuries are generally associated with incomplete restoration of motor function. The slow rate of nerve regeneration after injury may account for this. Although many benefits of resveratrol have been shown in the nervous system, it is not clear whether resveratrol could promote fast nerve regeneration and motor repair after peripheral nerve injury. This study showed that the motor deficits caused by sciatic nerve crush injury were alleviated by daily systematic resveratrol treatment within 10 days. Resveratrol increased the number of axons in the distal part of the injured nerve, indicating enhanced nerve regeneration. In the affected ventral spinal cord, resveratrol enhanced the expression of several vascular endothelial growth factor family proteins (VEGFs) and increased the phosphorylation of p300 through Akt signaling, indicating activation of p300 acetyltransferase. Inactivation of p300 acetyltransferase reversed the resveratrol-induced expression of VEGFs and motor repair in rats that had undergone sciatic nerve crush injury. The above results indicated that daily systematic resveratrol treatment promoted nerve regeneration and led to rapid motor repair. Resveratrol activated p300 acetyltransferase-mediated VEGF signaling in the affected ventral spinal cord, which may have thus contributed to the acceleration of nerve regeneration and motor repair.

Towards resolving the enigma of the dichotomy of resveratrol: cis- and trans-resveratrol have opposite effects on TyrRS-regulated PARP1 activation

“…Although SIRT1 is essential for coronavirus replication and survival [113], RSV instead inhibits coronavirus replication [112,113], and the acetylation of p53 is a critical mediator of antiviral response [244]. Interestingly, RSV treatment is known to activate p300 acetyltransferase to protect against rat spinal cord affected by sciatic nerve injury [245] and is also known to activate AMPK independent of SIRT1 in neurons [246] through yet unknown mechanisms. However, RSV activates AMPK in a poly-ADP-ribose polymerase 1 (PARP1)-dependent manner [71], which is also a potent inhibitor of SIRT1 [247].…”

Resveratrol Inhibits Venezuelan Equine Encephalitis Virus Infection by Interfering with the AKT/GSK Pathway

“…In one of our previous publications, we observed that VEEV infection would lead to more necrosis than apoptosis in the same glioblastoma cell line, U87MG, indicating that the neural damage induced by VEEV can be robust and irreversible [ 48 ]. On the other hand, the mechanisms of neurological improvement facilitated by resveratrol have been recently depicted in numerous pieces of literature, including enhancement of autophagy, anti-oxidant effectiveness, and direct nerve regeneration [ 49 , 50 , 51 ]. As a result, the neuroprotectivity of resveratrol is worthy of further investigation as it relates to VEEV infection.…”

Why is NMNAT Protective against Neuronal Cell Death and Axon Degeneration, but Inhibitory of Axon Regeneration?

“…The neuroprotective action of resveratrol, an allosteric activator of SIRT1 [97], is well known [98] and, in several cases, it has been demonstrated that it acts through SIRT1 in this regard [99,100]. Two recent reports have also indicated that resveratrol treatment promoted axon regeneration in different models [101,102]. Resveratrol has, however, a myriad of known cellular targets [103,104], and in the above cases, its role in axon regeneration was attributed to other molecules rather than SIRT1 activation.…”