Age‐dependent increase of perineuronal nets in the human hippocampus and precocious aging in epilepsy

作者：Annika Lehner, Lucas Hoffmann, Stefan Rampp, Roland Coras, Friedrich P. Paulsen, Renato Frischknecht, Hajo M. Hamer, Katrin Walther, Sebastian Brandner, Wiebke Hofer, Tom Pieper, Lea Marie Reisch, Christian G. Bien, Ingmar Blümcke · 发表于：Epilepsia Open · 年份：2024 · DOI：10.1002/epi4.12963 · 被引用次数：25 · 研究领域：Proteoglycans and glycosaminoglycans research、Neurogenesis and neuroplasticity mechanisms、Bone and Dental Protein Studies

OBJECTIVE: Perineuronal nets (PNN) are specialized extracellular matrix (ECM) components of the central nervous system, frequently accumulating at the surface of inhibitory GABAergic interneurons. While an altered distribution of PNN has been observed in neurological disorders including Alzheimer's disease, schizophrenia and epilepsy, their anatomical distribution also changes during physiological brain maturation and aging. Such an age-dependent shift was experimentally associated also with hippocampal engram formation during brain maturation. Our aim was to histopathologically assess PNN in the hippocampus of adult and pediatric patients with temporal lobe epilepsy (TLE) compared to age-matched post-mortem control subjects and to compare PNN-related changes with memory impairment observed in our patient cohort. METHODS: Sixty-six formalin-fixed and paraffin-embedded tissue specimens of the human hippocampus were retrieved from the European Epilepsy Brain Bank. Twenty-nine patients had histopathologically confirmed hippocampal sclerosis (HS), and eleven patients suffered from TLE without HS. PNN were immunohistochemically visualized using an antibody directed against aggrecan and manually counted from hippocampus subfields and the subiculum. RESULTS: PNN density increased with age in both human controls and TLE patients. However, their density was significantly higher in all HS patients compared to age-matched controls. Intriguingly, TLE patients presented presurgically with...