Temporal lobe epilepsy is associated with neuroinflammation, extracellular matrix remodeling, and synaptic protein alterations

Auer S, Hoffmann L, Schicht M, Blümcke I, Paulsen F (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Frontiers in Molecular Neuroscience Frontiers Research Foundation / Frontiers Media

Book Volume: 19

Article Number: 1728666

DOI: 10.3389/fnmol.2026.1728666

Abstract

focal epilepsy and is frequently associated with neuronal cell loss and astrogliosis in the hippocampus, i.e. hippocampal sclerosis (HS).Methods: In this study, we performed mass spectrometry-based proteomic profiling of microdissected hippocampal, neocortical, and white matter tissue obtained from TLE patients and respective control samples.Results: In hippocampal TLE tissue, we observed significant upregulation of proteins involved in complement system activation, extracellular matrix (ECM) organization, and astrocyte reactivity, indicative of active inflammatory remodeling within the sclerotic hippocampus. Conversely, synaptic proteins, including glutamate and gamma-aminobutyric acid (GABA) receptors, along with other regulators of synaptic structure and function, were markedly downregulated. Interestingly, in neocortical and white matter regions from the same TLE patients, immune- and ECM-related proteins were downregulated or unchanged, whereas synaptic proteins were preserved or upregulated.Discussion: These region-specific molecular signatures suggest that inflammatory-driven ECM remodeling is spatially restricted to the epileptogenic hippocampus, where it may contribute to synaptic destabilization and network dysfunction. Together, our findings support the hypothesis that inflammatory ECM remodeling in the hippocampus plays a central role in epileptogenesis in TLE. In contrast, the neocortical and white matter regions may undergo compensatory adaptions. The convergence of immune and ECM-related alterations on synaptic structures highlights a potential pathophysiological axis in epilepsy and points to novel molecular targets for therapeutic intervention.

Authors with CRIS profile

Sophia Auer Lehrstuhl für Funktionelle und Klinische Anatomie Lucas Hoffmann Institute of Neuropathology Martin Schicht Lehrstuhl für Funktionelle und Klinische Anatomie Ingmar Blümcke Lehrstuhl für Neuropathologie Friedrich Paulsen Lehrstuhl für Funktionelle und Klinische Anatomie

Additional Organisation(s)

Sonderforschungsbereich 1540/1 - Erforschung der Mechanik des Gehirns (EBM): Verständnis, Engineering und Nutzung mechanischer Eigenschaften und Signale in der Entwicklung, Physiologie und Pathologie des zentralen Nervensystems

How to cite

APA:

Auer, S., Hoffmann, L., Schicht, M., Blümcke, I., & Paulsen, F. (2026). Temporal lobe epilepsy is associated with neuroinflammation, extracellular matrix remodeling, and synaptic protein alterations. Frontiers in Molecular Neuroscience, 19. https://doi.org/10.3389/fnmol.2026.1728666

MLA:

Auer, Sophia, et al. "Temporal lobe epilepsy is associated with neuroinflammation, extracellular matrix remodeling, and synaptic protein alterations." Frontiers in Molecular Neuroscience 19 (2026).

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