Neurodevelopmental timing and socio-cognitive development in a prosocial cooperatively breeding primate ().

Primate brain development is shaped by inputs received during critical periods. These inputs differ between independent and cooperative breeders: In cooperative breeders, infants interact with multiple caregivers. We study how the neurodevelopmental timing of the cooperatively breeding common marmoset maps onto behavioral milestones.

Axon guidance during mouse central nervous system regeneration is required for specific brain innervation.

Reconstructing functional neuronal circuits is one major challenge of central nervous system repair. Through activation of pro-growth signaling pathways, some neurons achieve long-distance axon regrowth. Yet, functional reconnection has hardly been obtained, as these regenerating axons fail to resume their initial trajectory and reinnervate their proper target.

Brief and long maternal separation in C57Bl6J mice: behavioral consequences for the dam and the offspring.

Introduction: Animal models, especially rodents, have become instrumental to experimentally investigate the effects of an adverse post-natal environment on the developing brain. For this purpose, maternal separation (MS) paradigms have been widely used in the last decades. Nonetheless, how MS affects maternal behavior and, ultimately, the offspring depend on multiple variables.

Optimized miR-124 reporters uncover differences in miR-124 expression among neuronal populations .

Introduction: Although intensively studied in the last decades, how microRNAs (miRNAs) are expressed across different cell types in the brain remains largely unknown.

Materials: To address this issue, we sought to develop optimized fluorescence reporters that could be expressed in precise cellular subsets and used to accurately quantify miR contents .

Results: Focusing on miR-124, we tested different reporter designs whose efficiency was confirmed in different settings including cell lines and primary neuronal cultures from different brain structures.

Region-specific microRNA alterations in marmosets carrying SLC6A4 polymorphisms are associated with anxiety-like behavior.

Background: Psychiatric diseases such as depression and anxiety are multifactorial conditions, highly prevalent in western societies. Human studies have identified a number of high-risk genetic variants for these diseases. Among them, polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4) have attracted much attention.

Cholinergic interneuron inhibition potentiates corticostriatal transmission in direct medium spiny neurons and rescues motor learning in parkinsonism.

Striatal cholinergic interneurons (CINs) respond to salient or reward prediction-related stimuli after conditioning with brief pauses in their activity, implicating them in learning and action selection. This pause is lost in animal models of Parkinson's disease. How this signal regulates the striatal network remains an open question.

Social Isolation and Enrichment Induce Unique miRNA Signatures in the Prefrontal Cortex and Behavioral Changes in Mice.

An extensive body of evidence supports the notion that exposure to an enriched/impoverished environment alters brain functions via epigenetic changes. However, how specific modifications of social environment modulate brain functions remains poorly understood. To address this issue, we investigate the molecular and behavioral consequences of briefly manipulating social settings in young and middle-aged wild-type mice.

Deficits in Social Behavior Precede Cognitive Decline in Middle-Aged Mice.

An extensive literature details deterioration of multiple brain functions, especially memory and learning, during aging in humans and in rodents. In contrast, the decline of social functions is less well understood. It is presently not clear whether age-dependent deficits observed in social behavior mainly reflect the disruption of social networks activity or are simply secondary to a more general impairment of cognitive and executive functions in older individuals.

EMMPRIN overexpression in SVZ neural progenitor cells increases their migration towards ischemic cortex.

Stimulation of endogenous neurogenesis and recruitment of neural progenitors from the subventricular zone (SVZ) neurogenic site may represent a useful strategy to improve regeneration in the ischemic cortex. Here, we tested whether transgenic overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN), the regulator of matrix metalloproteinases (MMPs) expression, in endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ) could increase migration towards ischemic injury. For this purpose, we applied a lentivector-mediated gene transfer system.

Downregulation of the Host Gene jigr1 by miR-92 Is Essential for Neuroblast Self-Renewal in Drosophila.

Intragenic microRNAs (miRNAs), located mostly in the introns of protein-coding genes, are often co-expressed with their host mRNAs. However, their functional interaction in development is largely unknown. Here we show that in Drosophila, miR-92a and miR-92b are embedded in the intron and 3'UTR of jigr1, respectively, and co-expressed with some jigr1 isoforms.

Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemporal dementia.

Neurodegenerative diseases, such as frontotemporal dementia (FTD), are often associated with behavioral deficits, but the underlying anatomical and molecular causes remain poorly understood. Here we show that forebrain-specific expression of FTD-associated mutant CHMP2B in mice causes several age-dependent neurodegenerative phenotypes, including social behavioral impairments. The social deficits were accompanied by a change in AMPA receptor (AMPAR) composition, leading to an imbalance between Ca(2+)-permeable and Ca(2+)-impermeable AMPARs.

The emerging roles of microRNAs in the pathogenesis of frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) spectrum disorders.

Increasing evidence suggests that frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) share some clinical, pathological, and molecular features as part of a common neurodegenerative spectrum disorder. In recent years, enormous progress has been made in identifying both pathological proteins and genetic mutations associated with FTD-ALS. However, the molecular pathogenic mechanisms of disease onset and progression remain largely unknown.

Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons.

The recently identified GGGGCC repeat expansion in the noncoding region of C9ORF72 is the most common pathogenic mutation in patients with frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS). We generated a human neuronal model and investigated the pathological phenotypes of human neurons containing GGGGCC repeat expansions. Skin biopsies were obtained from two subjects who had >1,000 GGGGCC repeats in C9ORF72 and their respective fibroblasts were used to generate multiple induced pluripotent stem cell (iPSC) lines.

Cause or Effect: Misregulation of microRNA Pathways in Neurodegeneration.

During normal aging or neurodegenerative diseases, neuronal survival and function depend on protein homeostasis, which is regulated by multiple mechanisms, including the microRNA (miRNA) pathway. In different cells types, the absence of Dicer, a key miRNA processing enzyme, leads to neurodegeneration through cell-autonomous and non-cell-autonomous mechanisms. Loss of certain miRNAs also causes neurodegeneration in some model organisms.

MicroRNA-9: functional evolution of a conserved small regulatory RNA.

The functional significance of microRNA-9 (miR-9) during evolution is evidenced by its conservation at the nucleotide level from flies to humans but not its diverse expression patterns. Recent studies in several model systems reveal that miR-9 can regulate neurogenesis through its actions in neural or non-neural cell lineages. In vertebrates, miR-9 exerts diverse cell-autonomous effects on the proliferation, migration, and differentiation of neural progenitor cells by modulating different mRNA targets.

Heterogeneity in primary nociceptive neurons: from molecules to pathology.

Pain sensation (nociception) is an alarm system aiming to signal the presence of potentially or actually harmful stimuli. In our hazard-rich environment, pain initiates the necessary reactions to prevent or limit tissue damage in response to noxious inputs playing therefore a crucial survival role. Specialized noxious stimuli detectors, called primary nociceptive neurons or nociceptors transduce and convey pain information to the central nervous system.

Hepatocyte growth factor-Met signaling is required for Runx1 extinction and peptidergic differentiation in primary nociceptive neurons.

Nociceptors in peripheral ganglia display a remarkable functional heterogeneity. They can be divided into the following two major classes: peptidergic and nonpeptidergic neurons. Although RUNX1 has been shown to play a pivotal role in the specification of nonpeptidergic neurons, the mechanisms driving peptidergic differentiation remain elusive.

stac1 and stac2 genes define discrete and distinct subsets of dorsal root ganglia neurons.

Deciphering the precise in vivo function of a particular neuronal subpopulation is one of the most challenging issues in neurobiology. Dorsal root ganglia (DRG) neurons represent a powerful model system to address this fundamental question. These neurons display many morphological, anatomical and few molecular characteristics.

Fibroblast growth factor-2 overexpression in transplanted neural progenitors promotes perivascular cluster formation with a neurogenic potential.

Stem/progenitor cell-based therapies hold promises for repairing the damaged nervous system. However, the efficiency of these approaches for neuronal replacement remains very limited. A major challenge is to develop pretransplant cell manipulations that may promote the survival, engraftment, and differentiation of transplanted cells.

Adverse effects of methylene blue on the central nervous system.

Background: An increasing number of clinical observations suggest adverse neurologic outcome after methylene blue (MB) infusion in the setting of parathyroid surgery. Hence, the aim of the current study was to investigate the potentially neurotoxic effects of MB using a combination of in vivo and in vitro experimental approaches.

Methods: Isoflurane-anesthetized adult rats were used to evaluate the impact of a single bolus intravascular administration of MB on systemic hemodynamic responses and on the minimum alveolar concentration (MAC) of isoflurane using the tail clamp test.

Expression of FGF-2 in neural progenitor cells enhances their potential for cellular brain repair in the rodent cortex.

Strategies to enhance the capacity of grafted stem/progenitors cells to generate multipotential, proliferative and migrating pools of cells in the postnatal brain could be crucial for structural repair after brain damage. We investigated whether the over-expression of basic fibroblast growth factor 2 (FGF-2) in neural progenitor cells (NPCs) could provide a robust source of migrating NPCs for tissue repair in the rat cerebral cortex. Using live imaging we provide direct evidence that FGF-2 over-expression significantly enhances the migratory capacity of grafted NPCs in complex 3D structures, such as cortical slices.