Fructose-Driven glycolysis supports synaptic function in subterranean rodent - Gansu Zokor (Eospalax cansus)

Several studies indicate that fructose can be used as an energy source for subterranean rodents. However, how subterranean rodents utilize fructose metabolism with no apparent physiological drawbacks remains poorly understood. In the present study, we measured field excitatory postsynaptic potentials (fEPSPs) in hippocampal slices from Gansu zokor and SD rats hippocampi before and 60 min after replacement of 10 mM glucose in the artificial cerebrospinal fluid (ACSF) with 10 mM fructose (gassed with 95 % O₂ and 5 % CO₂). Subsequently, we performed transcriptome analysis on Gansu zokor brains incubated with ACSF containing 10 mM fructose and determined the contents of fructose, lactate, ATP, and UA. Whole brain RNA and proteins were extracted to detect the transcriptional levels of Glut5, Khk, Aldoc, and Cs and the translational levels of GLUT5, CS, NRF2, and c-FOS. The results showed that Gansu zokor brains exhibit higher levels of GLUT5 protein and Khk mRNA levels than SD rats to facilitate fructose uptake and metabolism, resulting in increased fructose, ATP, and lactate content in the brain during fructose incubation. Stable UA levels during fructose metabolism reduce the risk of oxidative stress and neuroinflammation, and activation of the Nrf2 pathway increases downstream antioxidant capacity, thereby reducing brain damage. Persistent fEPSP signaling suggests that fructose supports excitatory synaptic transmission in the CA1 region of the hippocampus of the Gansu zokor but leads to hippocampal dysfunction in SD rats. The unique insights about fructose metabolism in the brain of Gansu zokor obtained in our study will be useful for further studies on the evolution of subterranean rodents.