-derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility.

A hexanucleotide repeat expansion in the gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How this mutation leads to these neurodegenerative diseases remains unclear. Here, we show using patient stem cell-derived motor neurons that the repeat expansion impairs microtubule-based transport, a process critical for neuronal survival.

HDAC6 inhibition restores TDP-43 pathology and axonal transport defects in human motor neurons with TARDBP mutations.

TDP-43 is the major component of pathological inclusions in most ALS patients and in up to 50% of patients with frontotemporal dementia (FTD). Heterozygous missense mutations in TARDBP, the gene encoding TDP-43, are one of the common causes of familial ALS. In this study, we investigate TDP-43 protein behavior in induced pluripotent stem cell (iPSC)-derived motor neurons from three ALS patients with different TARDBP mutations, three healthy controls and an isogenic control.

Differentiation but not ALS mutations in FUS rewires motor neuron metabolism.

Energy metabolism has been repeatedly linked to amyotrophic lateral sclerosis (ALS). Yet, motor neuron (MN) metabolism remains poorly studied and it is unknown if ALS MNs differ metabolically from healthy MNs. To address this question, we first performed a metabolic characterization of induced pluripotent stem cells (iPSCs) versus iPSC-derived MNs and subsequently compared MNs from ALS patients carrying FUS mutations to their CRISPR/Cas9-corrected counterparts.

Generation of a human induced pluripotent stem cell-based model for tauopathies combining three microtubule-associated protein TAU mutations which displays several phenotypes linked to neurodegeneration.

Introduction: Tauopathies are neurodegenerative diseases characterized by TAU protein-related pathology, including frontotemporal dementia and Alzheimer's disease among others. Mutant TAU animal models are available, but none of them faithfully recapitulates human pathology and are not suitable for drug screening.

Methods: To create a new in vitro tauopathy model, we generated a footprint-free triple MAPT-mutant human induced pluripotent stem cell line (N279K, P301L, and E10+16 mutations) using clustered regularly interspaced short palindromic repeats-FokI and piggyBac transposase technology.

Experimental febrile seizures increase dendritic complexity of newborn dentate granule cells.

Objective: Febrile seizures (FS) are fever-associated convulsions, being the most common seizure disorder in early childhood. A subgroup of these children later develops epilepsy characterized by a hyperexcitable neuronal network in the hippocampus. Hippocampal excitability is regulated by the hippocampal dentate gyrus (DG) where postnatal neurogenesis occurs.

Neuropeptides as targets for the development of anticonvulsant drugs.

Epilepsy is a common neurological disorder characterized by recurrent seizures. These seizures are due to abnormal excessive and synchronous neuronal activity in the brain caused by a disruption of the delicate balance between excitation and inhibition. Neuropeptides can contribute to such misbalance by modulating the effect of classical excitatory and inhibitory neurotransmitters.

Validation of reference genes for quantitative real-time PCR studies in the dentate gyrus after experimental febrile seizures.

Background: Quantitative real-time PCR (qPCR) is a commonly used technique to quantify gene expression levels. Validated normalization is essential to obtain reliable qPCR data. In that context, normalizing to multiple reference genes has become the most popular method.

Experimental early-life febrile seizures induce changes in GABA(A) R-mediated neurotransmission in the dentate gyrus.

Purpose:   Febrile seizures (FS), the most frequent seizure type during childhood, have been linked to temporal lobe epilepsy (TLE) in adulthood. Yet, underlying mechanisms are still largely unknown. Altered γ-aminobutyric acid (GABA)ergic neurotransmission in the dentate gyrus (DG) circuit has been hypothesized to be involved.

Long-lasting enhancement of GABA(A) receptor expression in newborn dentate granule cells after early-life febrile seizures.

Febrile seizures (FS) are the most common type of seizures in childhood and are suggested to play a role in the development of temporal lobe epilepsy (TLE). Animal studies demonstrated that experimental FS induce a long-lasting change in hippocampal excitability, resulting in enhanced seizure susceptibility. Hippocampal neurogenesis and altered ion channel expression have both been proposed as mechanisms underlying this decreased seizure threshold.

Potential role for ligand-gated ion channels after seizure-induced neurogenesis.

Epileptic seizures result in an increased generation of new neurons in the dentate gyrus of the adult mammalian hippocampus. The role of these seizure-induced newborn neurons in the process of epileptogenesis remains largely unknown. Recent work, however, suggests an aberrant incorporation of newborn cells into the existing hippocampal network in such a way that they promote hippocampal hyperexcitability.