Aberrant generation of dentate gyrus granule cells is associated with epileptic susceptibility in p53 conditional knockout mice.

Neuronal apoptosis is a mechanism used to clear the cells of oxidative stress or DNA damage and refine the final number of neurons for a functional neuronal circuit. The tumor suppressor protein p53 is a key regulator of the cell cycle and serves as a checkpoint for eliminating neurons with high DNA damage, hyperproliferative signals or cellular stress. During development, p53 is largely expressed in progenitor cells.

Piezo1 Is Required for Myoblast Migration and Involves Polarized Clustering in Association with Cholesterol and GM1 Ganglioside.

A specific plasma membrane distribution of the mechanosensitive ion channel Piezo1 is required for cell migration, but the mechanism remains elusive. Here, we addressed this question using WT and -silenced C2C12 mouse myoblasts and WT and -KO human kidney HEK293T cells. We showed that cell migration in a cell-free area and through a porous membrane decreased upon silencing or deletion, but increased upon Piezo1 activation by Yoda1, whereas migration towards a chemoattractant gradient was reduced by Yoda1.

Conditional deletion of KCC2 impairs synaptic plasticity and both spatial and nonspatial memory.

The postsynaptic inhibition through GABA receptors (GABAR) relies on two mechanisms, a shunting effect due to an increase in the postsynaptic membrane conductance and, in mature neurons, a hyperpolarization effect due to an entry of chloride into postsynaptic neurons. The second effect requires the action of the K-Cl cotransporter KCC2 which extrudes Cl from the cell and maintains its cytosolic concentration very low. Neuronal chloride equilibrium seems to be dysregulated in several neurological and psychiatric conditions such as epilepsy, anxiety, schizophrenia, Down syndrome, or Alzheimer's disease.

Inhibitory synapse dysfunction and epileptic susceptibility associated with KIF2A deletion in cortical interneurons.

Malformation of cortical development (MCD) is a family of neurodevelopmental disorders, which usually manifest with intellectual disability and early-life epileptic seizures. Mutations in genes encoding microtubules (MT) and MT-associated proteins are one of the most frequent causes of MCD in humans. KIF2A is an atypical kinesin that depolymerizes MT in ATP-dependent manner and regulates MT dynamics.

KIF2A deficiency causes early-onset neurodegeneration.

KIF2A is an atypical kinesin that has the capacity to depolymerize microtubules. Patients carrying mutations in KIF2A suffer from progressive microcephaly and mental disabilities. While the role of this protein is well documented in neuronal migration, the relationship between its dysfunction and the pathobiology of brain disorders is unclear.

A TRPM7 mutation linked to familial trigeminal neuralgia: Omega current and hyperexcitability of trigeminal ganglion neurons.

Trigeminal neuralgia (TN) is a unique pain disorder characterized by intense paroxysmal facial pain within areas innervated by the trigeminal nerve. Although most cases of TN are sporadic, familial clusters of TN suggest that genetic factors may contribute to this disorder. Whole-exome sequencing in patients with TN reporting positive family history demonstrated a spectrum of variants of ion channels including TRP channels.

Thermosensitive receptors in neural stem cells link stress-induced hyperthermia to impaired neurogenesis via microglial engulfment.

Social stress impairs hippocampal neurogenesis and causes psychiatric disorders such as depression. Recent studies have highlighted the significance of increased body temperature in stress responses; however, whether and how social stress–induced hyperthermia affects hippocampal neurogenesis remains unknown. Here, using transgenic mice in which the thermosensitive transient receptor potential vanilloid 4 (TRPV4) is conditionally knocked out in Nestin-expressing neural stem cells (NSCs), we found that social defeat stress (SDS)–induced hyperthermia activates TRPV4 in NSCs in the dentate gyrus and thereby impairs hippocampal neurogenesis.

Overexpression of wild-type human amyloid precursor protein alters GABAergic transmission.

The function of the amyloid precursor protein (APP) is not fully understood, but its cleavage product amyloid beta (Aβ) together with neurofibrillary tangles constitute the hallmarks of Alzheimer's disease (AD). Yet, imbalance of excitatory and inhibitory neurotransmission accompanied by loss of synaptic functions, has been reported much earlier and independent of any detectable pathological markers. Recently, soluble APP fragments have been shown to bind to presynaptic GABA receptors (GABARs), subsequently decreasing the probability of neurotransmitter release.

Regulation of PPARα by APP in Alzheimer disease affects the pharmacological modulation of synaptic activity.

Among genetic susceptibility loci associated with late-onset Alzheimer disease (LOAD), genetic polymorphisms identified in genes encoding lipid carriers led to the hypothesis that a disruption of lipid metabolism could promote disease progression. We previously reported that amyloid precursor protein (APP) involved in Alzheimer disease (AD) physiopathology impairs lipid synthesis needed for cortical networks' activity and that activation of peroxisome proliferator-activated receptor α (PPARα), a metabolic regulator involved in lipid metabolism, improves synaptic plasticity in an AD mouse model. These observations led us to investigate a possible correlation between PPARα function and full-length APP expression.

Trigeminal Neuralgia TRPM8 Mutation: Enhanced Activation, Basal [Ca] and Menthol Response.

Objective: To assess the functional effects of a variant, c.89 G > A (p.Arg30Gln), in the transient receptor potential melastatin 8 (TRPM8) cold-sensing, nonselective cation channel, which we have previously identified in a patient with familial trigeminal neuralgia.

DIAPH3 deficiency links microtubules to mitotic errors, defective neurogenesis, and brain dysfunction.

Diaphanous (DIAPH) three (DIAPH3) is a member of the formin proteins that have the capacity to nucleate and elongate actin filaments and, therefore, to remodel the cytoskeleton. DIAPH3 is essential for cytokinesis as its dysfunction impairs the contractile ring and produces multinucleated cells. Here, we report that DIAPH3 localizes at the centrosome during mitosis and regulates the assembly and bipolarity of the mitotic spindle.

Mechanical activation of TRPV4 channels controls albumin reabsorption by proximal tubule cells.

Defects in protein reabsorption by the proximal tubule are toxic for epithelial cells in the nephron and may result in nephropathy. In this study, we showed that the ion channel TRPV4 modulated the endocytosis of albumin and low-molecular weight proteins in the proximal tubule. TRPV4 was found at the basolateral side of proximal tubule cells, and its mechanical activation by cell stretching induced Ca entry into the cytosol, which promoted endocytosis.

Correction: Gualdani, R.; et al. Store-Operated Calcium Entry Contributes to Cisplatin-Induced Cell Death in Non-Small Cell Lung Carcinoma. 2019, , 430.

The authors wish to make the following corrections to this paper [...

How TRPC Channels Modulate Hippocampal Function.

Transient receptor potential canonical (TRPC) proteins constitute a group of receptor-operated calcium-permeable nonselective cationic membrane channels of the TRP superfamily. They are largely expressed in the hippocampus and are able to modulate neuronal functions. Accordingly, they have been involved in different hippocampal functions such as learning processes and different types of memories, as well as hippocampal dysfunctions such as seizures.

Amyloid Precursor Protein (APP) Controls the Expression of the Transcriptional Activator Neuronal PAS Domain Protein 4 (NPAS4) and Synaptic GABA Release.

The amyloid precursor protein (APP) has been extensively studied as the precursor of the β-amyloid (Aβ) peptide, the major component of the senile plaques found in the brain of Alzheimer's disease (AD) patients. However, the function of APP per se in neuronal physiology remains to be fully elucidated. APP is expressed at high levels in the brain.

Role of the TRPC1 Channel in Hippocampal Long-Term Depression and in Spatial Memory Extinction.

Group I metabotropic glutamate receptors (mGluR) are involved in various forms of synaptic plasticity that are believed to underlie declarative memory. We previously showed that mGluR5 specifically activates channels containing TRPC1, an isoform of the canonical family of Transient Receptor Potential channels highly expressed in the CA1-3 regions of the hippocampus. Using a tamoxifen-inducible conditional knockout model, we show here that the acute deletion of the gene alters the extinction of spatial reference memory.

Light entrainment of retinal biorhythms: cryptochrome 2 as candidate photoreceptor in mammals.

The mechanisms that synchronize the biorhythms of the mammalian retina with the light/dark cycle are independent of those synchronizing the rhythms in the central pacemaker, the suprachiasmatic nucleus. The identity of the photoreceptor(s) responsible for the light entrainment of the retina of mammals is still a matter of debate, and recent studies have reported contradictory results in this respect. Here, we suggest that cryptochromes (CRY), in particular CRY 2, are involved in that light entrainment.

TRPV4 channel mediates adventitial fibroblast activation and adventitial remodeling in pulmonary hypertension.

Pulmonary arterial adventitial fibroblasts (PAF), the most abundant cellular constituent of adventitia, act as a key regulator of pulmonary vascular wall structure and function from the outside-in. Previous studies indicate that transient receptor potential vanilloid 4 (TRPV4) channel plays an important role in the development of pulmonary hypertension (PH), but no attention has been given so far to its role in adventitial remodeling. In this study, we thus investigated TRPV4 implication in PAF activation occurring in PH.

Silane influence on bonding to CAD-CAM composites: An interfacial fracture toughness study.

Objectives: To evaluate silane influence on the interfacial fracture toughness (IFT) of composite cement, with the two sub-classes of CAD-CAM composites, polymer-infiltrated ceramic networks (PICN) and dispersed fillers (DF), after hydrofluoric acid etching (HF) or airborne-particle abrasion (AB). A secondary objective was to correlate results with developed interfacial area ratio (Sdr) and surface wettability.

Methods: Experimental PICN and DF blocks were cut into equilateral half-prisms, which were treated with HF or AB, then treated with an experimental silane or not and bonded to their counterparts with an experimental light-cure resin cement.

Store-Operated Calcium Entry Contributes to Cisplatin-Induced Cell Death in Non-Small Cell Lung Carcinoma.

Cisplatin (CDDP) is one of the principal chemotherapeutic agents used for the first-line treatment of many malignancies, including non-small cell lung carcinoma (NSCLC). Despite its use for over 40 years, its mechanism of action is not yet fully understood. Store-operated calcium entry (SOCE), the main pathway allowing Ca entry in non-excitable cells, is involved in tumorogenesis, cancer progression and chemoresistance.

Corrigendum: Low-Light Dependence of the Magnetic Field Effect on Cryptochromes: Possible Relevance to Plant Ecology.

[This corrects the article DOI: 10.3389/fpls.2018.