The effect of Pyrroloquinoline quinone and Resveratrol on the Survival and Regeneration of Cerebellar Granular Neurons

Abstract

The inability of central nervous system (CNS) to regenerate following traumatic brain injury (TBI) can be attributed to apoptotic cell death, inhibitory extrinsic environment, and the limited ability of neurons to regenerate. Thus, fostering the intrinsic regenerative potential and minimizing neuronal cell death could be a promising therapeutic approach. Pyrroloquinoline quinone (PQQ) was previously reported for its neuroprotective and regenerative potential on peripheral nerves. Here, we investigated the ability of PQQ to induce neurite re-growth in a wound healing model on cultured cerebellar granular neurons (CGNs), an integral part of cerebellar circuitry, as one of the most affected areas following TBI. The neuroprotective effect was also examined utilizing K⁺/FCS deprivation-induced apoptosis model in CGNs. Resveratrol (RVT), an effective promoter of neuroprotection and regeneration both centrally and peripherally was also investigated separately and in combination with PQQ to establish a possible synergistic effect. RVT (5 μM) and PQQ (0.5 μM) showed a tendency to promote neurite re-growth in the wound healing assay, however the effect observed was statistically insignificant. Higher concentrations of PQQ (1 and 2 μM) were found to be less effective. Resveratrol did not affect neurite length in CGNs culture; however, it did significantly increase the number of viable CGNs. For the neuroprotective effect; PQQ and RVT showed a significant increase in the survival of CGNs following K⁺/FCS deprivation of culture. Thus, both compounds showed a tendency to support neurite outgrowth in addition to a significant neuroprotective effect, but no synergistic effect was detected.

Keywords: Cerebellar granular neurons; Neurite outgrowth; Neuroprotection; Neuroregeneration; Pyrroloquinoline quinone; Resveratrol.