Putative long-range mossy fiber sprouting and regional hypermetabolic capacity in the hippocampus of patients with mesial temporal lobe epilepsy

Tu, T.; Wan, L.; Zhang, Q.-L.; Yang, C.; Zhou, H.; Sun, Z.; Long, H.-Y.; Tang, B.; Pan, A.; Tu, E.; Wang, J.; Yang, Z.-Q.; Li, Z.-Y.; Yan, X.-X.

doi:10.1101/2025.07.17.665452

bioRxiv · 10.1101/2025.07.17.665452

Putative long-range mossy fiber sprouting and regional hypermetabolic capacity in the hippocampus of patients with mesial temporal lobe epilepsy

Tu, T.·Wan, L.·Zhang, Q.-L.·Yang, C.·Zhou, H.·Sun, Z.·Long, H.-Y.·Tang, B.·Pan, A.·Tu, E.·Wang, J.·Yang, Z.-Q.·Li, Z.-Y.·Yan, X.-X.

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Abstract

Mesial temporal lobe epilepsy (MTLE) is pathologically characterized by neuronal loss in the dentate hilus, CA3 and CA1 regions, and mossy fiber (MF) sprouting into the inner molecular layer (iML). The latter forms aberrant excitatory circuities that are considered to facilitate recurrent seizures, with the subiculum also being related to epileptogenic activation. We recently identified a distinct expression of -smooth muscle actin (SMA) at the MF terminals in human hippocampus. This prompted us to explore MF sprouting in resected hippocampi (n=20) from patients with MTLE relative to postmortem control (n=20) using SMA along with reference markers for pathological cross-validation. Compared to control, neuronal loss assessed with neuron-specific nuclear antigen and sortilin immunolabeling reached CA1 in all resected hippocampi. SMA, zinc transporter 3 and {beta}-secretase 1 immunolabeling in the iML tended to be increased. The MF-related markers also revealed a preserved fibrous band extending across CA1 to subiculum. Cytochrome c oxidase immunolabeling also increased in iML and subiculum in the MTLE group. Taking together, the current findings point to the existence of long-range MF sprouting and a regional hypermetabolic compacity in the hippocampal formation of patients with drug resistant MTLE.

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Tu, T., Wan, L., Zhang, Q.-L., Yang, C., Zhou, H., Sun, Z., Long, H.-Y., Tang, B., Pan, A., Tu, E., Wang, J., Yang, Z.-Q., Li, Z.-Y., Yan, X.-X.. 2025-07-22. Putative long-range mossy fiber sprouting and regional hypermetabolic capacity in the hippocampus of patients with mesial temporal lobe epilepsy. https://doi.org/10.1101/2025.07.17.665452

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