Considering the Role of Extracellular Matrix Molecules, in Particular Reelin, in Granule Cell Dispersion Related to Temporal Lobe Epilepsy

Abstract

The extracellular matrix (ECM) of the nervous system can be considered as a dynamically adaptable compartment between neuronal cells, in particular neurons and glial cells, that participates in physiological functions of the nervous system. It is mainly composed of carbohydrates and proteins that are secreted by the different kinds of cell types found in the nervous system, in particular neurons and glial cells, but also other cell types, such as pericytes of capillaries, ependymocytes and meningeal cells. ECM molecules participate in developmental processes, synaptic plasticity, neurodegeneration and regenerative processes. As an example, the ECM of the hippocampal formation is involved in degenerative and adaptive processes related to epilepsy. The role of various components of the ECM has been explored extensively. In particular, the ECM protein reelin, well known for orchestrating the formation of neuronal layer formation in the cerebral cortex, is also considered as a player involved in the occurrence of postnatal granule cell dispersion (GCD), a morphologically peculiar feature frequently observed in hippocampal tissue from epileptic patients. Possible causes and consequences of GCD have been studied in various in vivo and in vitro models. The present review discusses different interpretations of GCD and different views on the role of ECM protein reelin in the formation of this morphological peculiarity.

ΔFosB is part of a homeostatic mechanism that protects the epileptic brain from further deterioration

“…Frontiers in Molecular Neuroscience 14 frontiersin.org Clasadonte et al 10.3389/fnmol.2023.1324922 evidence in the literature supports the role of Reelin in granule cell dispersion related to TLE (Leifeld et al, 2022). Reelin is a secreted glycoprotein present in the extracellular matrix that acts as a stop signal for neuronal migration during development (Tissir and Goffinet, 2003) but its function in adult hippocampus is not studied.…”

The role of dendritic spines in epileptogenesis

“…Granule cells in epilepsy models are known to undergo significant change. These changes include mossy fiber sprouting, migration to ectopic locations, and formation of new, disorganized dendrites ( Hester and Danzer, 2014 ; Leifeld et al, 2022 ). These mossy fiber changes are related to dendritic spine morphological changes, as development of new widely spread dendrites and creation of new dendritic spines with increased density in areas proximal to mossy fiber sprouting are observed during migration of developing granule cells ( Puhahn-Schmeiser et al, 2022 ).…”

Reelin Regulates Developmental Desynchronization Transition of Neocortical Network Activity

“…It controls neuronal migration and layer formation in the developing cerebral cortex, as evidenced by morphological studies on reeler mutant mice that lack reelin expression [36,37]. Reelin also modulates synaptic plasticity in the adult brain [38,39]. It has been shown that in the absence of reelin, experience-dependent plasticity in the visual cortex into adulthood was prolonged [40].…”