Sublayer- and cell-type-specific neurodegenerative transcriptional trajectories in hippocampal sclerosis.

Hippocampal sclerosis, the major neuropathological hallmark of temporal lobe epilepsy, is characterized by different patterns of neuronal loss. The mechanisms of cell-type-specific vulnerability and their progression and histopathological classification remain controversial. Using single-cell electrophysiology in vivo and immediate-early gene expression, we reveal that superficial CA1 pyramidal neurons are overactive in epileptic rodents.

SynGAP splice variants display heterogeneous spatio-temporal expression and subcellular distribution in the developing mammalian brain.

The SynGAP protein is a major regulator of synapse biology and neural circuit function. Genetic variants linked to epilepsy and intellectual disability disrupt synaptic function and neural excitability. SynGAP has been involved in multiple signaling pathways and can regulate small GTPases with very different roles.

SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse.

Synapses are fundamental information-processing units of the brain, and synaptic dysregulation is central to many brain disorders ("synaptopathies"). However, systematic annotation of synaptic genes and ontology of synaptic processes are currently lacking. We established SynGO, an interactive knowledge base that accumulates available research about synapse biology using Gene Ontology (GO) annotations to novel ontology terms: 87 synaptic locations and 179 synaptic processes.

Metazoan evolution of glutamate receptors reveals unreported phylogenetic groups and divergent lineage-specific events.

Glutamate receptors are divided in two unrelated families: ionotropic (iGluR), driving synaptic transmission, and metabotropic (mGluR), which modulate synaptic strength. The present classification of GluRs is based on vertebrate proteins and has remained unchanged for over two decades. Here we report an exhaustive phylogenetic study of GluRs in metazoans.

Synaptic proteomics as a means to identify the molecular basis of mental illness: Are we getting there?

Synapses are centrally involved in many brain disorders, particularly in psychiatric and neurodevelopmental ones. However, our current understanding of the proteomic alterations affecting synaptic performance in the majority of mental illnesses is limited. As a result, novel pharmacotherapies with improved neurological efficacy have been scarce over the past decades.

Evolution of complexity in the zebrafish synapse proteome.

The proteome of human brain synapses is highly complex and is mutated in over 130 diseases. This complexity arose from two whole-genome duplications early in the vertebrate lineage. Zebrafish are used in modelling human diseases; however, its synapse proteome is uncharacterized, and whether the teleost-specific genome duplication (TSGD) influenced complexity is unknown.

Telomere homeostasis in mammalian germ cells: a review.

Telomeres protect against genome instability and participate in chromosomal movements during gametogenesis, especially in meiosis. Thus, maintaining telomere structure and telomeric length is essential to both cell integrity and the production of germ cells. As a result, alteration of telomere homeostasis in the germ line may result in the generation of aneuploid gametes or gametogenesis disruption, triggering fertility problems.

Telomere homeostasis is compromised in spermatocytes from patients with idiopathic infertility.

Objective: To study whether the telomere structure of germ cells from idiopathic infertile men is altered and if this impairment is influenced by meiotic recombination and telomere length.

Design: We performed a detailed analysis of both telomeric repeat-containing RNA (TERRA) and telomerase distribution in testis cell spreads by combining immunofluorescence and RNA fluorescent in situ hybridization. In addition we analyzed meiotic recombination between homologous chromosomes by immunofluorescence and telomere length by quantitative fluorescent in situ hybridization.

Telomeric repeat-containing RNA (TERRA) and telomerase are components of telomeres during mammalian gametogenesis.

Telomeres are ribonucleoprotein structures at the end of chromosomes composed of telomeric DNA, specific-binding proteins, and noncoding RNA (TERRA). Despite their importance in preventing chromosome instability, little is known about the cross talk between these three elements during the formation of the germ line. Here, we provide evidence that both TERRA and the telomerase enzymatic subunit (TERT) are components of telomeres in mammalian germ cells.

Telomeric repeat-containing RNA and telomerase in human fetal oocytes.

Study Question: What is the distribution of telomeric repeat-containing RNA (TERRA) and of telomerase in human fetal oocytes?

Summary Answer: TERRA forms discrete foci at telomeres of human fetal oocytes and it co-localizes with both the shelterin component telomeric repeat-binding factor 2 (TRF2) and the catalytic subunit of human telomerase at the telomeres of meiotic chromosomes.

What Is Known Already: TERRA is a structural element of the telomeric chromatin that has been described in somatic cells of many different eukaryote species. The telomerase enzyme is inactive in adult somatic cells but is active in germ cells, stem cells and in the majority of tumors; however, its distribution in oocytes is still unknown.