Dendritic spine loss in epileptogenic Type II focal cortical dysplasia: Role of enhanced classical complement pathway activation

Dendritic spines are the postsynaptic sites for most excitatory glutamatergic synapses. We previously demonstrated a severe spine loss and synaptic reorganization in human neocortices presenting Type II focal cortical dysplasia (FCD), a developmental malformation and frequent cause of drug‐resistant focal epilepsy. We extend the findings, investigating the potential role of complement components C1q and C3 in synaptic pruning imbalance. Data from Type II FCD were compared with those obtained in focal epilepsies with different etiologies. Neocortical tissues were collected from 20 subjects, mainly adults with a mean age at surgery of 31 years, admitted to epilepsy surgery with a neuropathological diagnosis of: cryptogenic, temporal lobe epilepsy with hippocampal sclerosis, and Type IIa/b FCD. Dendritic spine density quantitation, evaluated in a previous paper using Golgi impregnation, was available in a subgroup. Immunohistochemistry, in situ hybridization, electron microscopy, and organotypic cultures were utilized to study complement/microglial activation patterns. FCD Type II samples presenting dendritic spine loss were characterized by an activation of the classical complement pathway and microglial reactivity. In the same samples, a close relationship between microglial cells and dendritic segments/synapses was found. These features were consistently observed in Type IIb FCD and in 1 of 3 Type IIa cases. In other patient groups and in perilesional areas outside the dysplasia, not presenting spine loss, these features were not observed. In vitro treatment with complement proteins of organotypic slices of cortical tissue with no sign of FCD induced a reduction in dendritic spine density. These data suggest that dysregulation of the complement system plays a role in microglia‐mediated spine loss. This mechanism, known to be involved in the removal of redundant synapses during development, is likely reactivated in Type II FCD, particularly in Type IIb; local treatment with anticomplement drugs could in principle modify the course of disease in these patients

Eps8 Regulates Axonal Filopodia in Hippocampal Neurons in Response to Brain-Derived Neurotrophic Factor (BDNF)

A novel signaling cascade controlling actin polymerization in response to extracellular signals regulates filopodia formation and likely also neuronal synapse formation

Ruolo dell'apoptosi e dell'inibizione di protein chinasi da parte di derivati isochinosulfonamidici in modelli in vitro di neurotossicita'

Dottorato di ricerca in tossicologia dell'ambiente e dell'alimentazione. 7. ciclo. Coordinatore F. Cattabeni. Coordinatore F. Cattabeni. Docente guida G. RacagniConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Legislative Documents

Also, variously referred to as: House bills; House documents; House legislative documents; legislative documents; General Court documents

Axon markers SMI31 and tau in multi-neuritic neurons.

<p>(A-D) Confocal images of hippocampal neurons co-transfected with control (A₁-D₁), a-SMN (A₂-D₃) or FL-SMN (A₄-D₅) specific siRNAs and the Venus plasmid (green, A₁-A₅ and C₁-C₅), fixed at 3DIV and labeled with the axonal markers SMI31 (blue, B₁-B₅) or tau (red, D₁-D₅). While neurons transfected with control siRNA had a single axon labeled by SMI31(A₁-B₁), in a-SMN and FL-SMN-silenced neurons displaying multi-neuritic morphology, SMI31or tau axonal staining was mainly in soma (B₅, D₂, D₄) or variably localized in two or more neuritic processes (B₂-B₄, D₃, D₅). (E) Quantification of axon labeling in individual multi-neuritic neurons. Stacked histograms showing SMI31 distribution in a-SMN and FL-SMN silenced neurons with multi-neuritic morphology. Data are presented as mean ± SEM. At least 70 cells from three different experiments were analyzed. Percent ratio of axonal markers distribution (multineurites/ only soma/axonal labeling) was compared by means of chi-square test (** p<0.01) between the two experimental conditions (a-SMN or FL-SMN siRNA). Scale bar: 10 μm.</p