Reduced exploration capacity despite brain volume increase in warm-acclimated common minnow

While evidence suggests that warming may impact cognition of ectotherms, the underlying mechanisms remain poorly understood. A possible but rarely considered mechanism is that the metabolic response of ectotherms to warming is associated with changes in brain morphology and function. Here, we compared aerobic metabolism, brain volume, boldness and accuracy of maze solving of common minnows (Phoxinus phoxinus) acclimated for 8 months to either their current optimal natural (14°C) or warm (20°C) water temperature. Metabolic rates indicated increased energy expenditure in warm-acclimated fish, but also at least partial thermal compensation as warm-acclimated fish maintained high aerobic scope. Warm-acclimated fish had larger brains than cool-acclimated fish. The volume of the dorsal medulla relative to the overall brain size was larger in warm- than in cool-acclimated fish, but the proportion of other brain regions did not differ between the temperature treatments. Warm-acclimated fish did not differ in boldness but made more errors than cool-acclimated fish in exploring the maze across four trials. Inter-individual differences in the number of exploration errors were repeatable across the four trials of the maze test. Our findings suggest that in warm environments, maintaining a high aerobic scope, which is important for the performance of physically demanding tasks, can come at the cost of changes in brain morphology and impairment of the capacity to explore novel environments. This trade-off could have strong fitness implications for wild ectotherms

3D phenotyping and QTL analysis of a complex character: rose bush architecture

Plant shape, and thereby plant architecture, is a major component of the visual quality of ornamental plants. We have been developing a new method for analyzing the entire plant architecture by 3D digitalization that allows an almost exhaustive description of rose bush architecture and generates a large number of variables, many of them inaccessible manually. We carried out a QTL analysis using this original phenotyping method. In order to evaluate a broader allelic variability as well as the effect of the genetic background on QTL detection, we used two connected, segregating, recurrent blooming populations. The number of QTLs per variable varied from three for the number of determined axes (NbDetA) to seven for the branching angle of order 2 long axes (AngLA2), the two populations taken together. Five new QTLs, located on the linkage groups (LGs) 2, 6, and 7, were detected for the branching angle of axes, and the QTL located on LG7 co-localized with RhBRC1, a branching repressor. Branching and stem elongation QTLs also co-located with RhBRC1, suggesting its pleiotropic nature. Year-specific QTLs were also revealed, that explained the genotype × year interactions observed for the number of order 3 short axes (NbSA3) and AngLA2 from a genetic point of view. We also evidenced an effect of the genetic background on QTL detection. This new knowledge should help to better reason the genetic improvement programs for rose bush architecture and, therefore, rose bush shape

Plant responses to red and far-red lights, applications in horticulture

Light drives plant growth and development, so its control is increasingly used as an environment-friendly tool to manage horticultural crops. However, this implies a comprehensive view of the main physiological processes under light control, and bridging knowledge gaps. This review presents the state of the art in i) perception of red (R) and far-red (FR) wavelengths and of the R:FR ratio by plants, ii) phenotypic plant responses, and iii) the molecular mechanisms related to these responses. Changes in red or far red radiation and R:FR ratios are perceived by phytochromes. Phytochrome-mediated regulation is complex and specific to each physiological process. Our review presents the effects of red and far-red lights on germination, aerial architectural development, flowering, photosynthesis and plant nutrition. It also addresses how red and far-red radiations interact with tolerance to drought, pathogens and herbivores. Current knowledge about the mechanisms whereby red, far-red and R:FR regulate these different processes is presented. The specific actors of light signal transduction are better known for germination or flowering than for other processes such as internode elongation or bud outgrowth. The phenotypic response to red, far-red and R:FR can vary among species, but also with growing conditions. The mechanisms underlying these differences in plant responses still need to be unveiled. Current knowledge about plants\u27 response to light is being applied in horticulture to improve crop yield and quality. To that purpose, it is now possible to manipulate light quality thanks to recent technological evolutions such as the development of photo-selective films and light-emitting diodes

Cellular injury and neuroinflammation in children with chronic intractable epilepsy

<p>Abstract</p> <p>Objective</p> <p>To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery.</p> <p>Methods</p> <p>Cortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6), encephalomalacia (5), Rasmussen's encephalitis (1) or mesial temporal lobe epilepsy (1). Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases.</p> <p>Results</p> <p>Marked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy.</p> <p>Conclusions</p> <p>Our results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy.</p

Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures

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CXCL12-Mediated Guidance of Migrating Embryonic Stem Cell-Derived Neural Progenitors Transplanted into the Hippocampus

Stem cell therapies for neurodegenerative disorders require accurate delivery of the transplanted cells to the sites of damage. Numerous studies have established that fluid injections to the hippocampus can induce lesions in the dentate gyrus (DG) that lead to cell death within the upper blade. Using a mouse model of temporal lobe epilepsy, we previously observed that embryonic stem cell-derived neural progenitors (ESNPs) survive and differentiate within the granule cell layer after stereotaxic delivery to the DG, replacing the endogenous cells of the upper blade. To investigate the mechanisms for ESNP migration and repair in the DG, we examined the role of the chemokine CXCL12 in mice subjected to kainic acid-induced seizures. We now show that ESNPs transplanted into the DG show extensive migration through the upper blade, along the septotemporal axis of the hippocampus. Seizures upregulate CXCL12 and infusion of the CXCR4 antagonist AMD3100 by osmotic minipump attenuated ESNP migration. We also demonstrate that seizures promote the differentiation of transplanted ESNPs toward neuronal rather than astrocyte fates. These findings suggest that ESNPs transplanted into the adult rodent hippocampus migrate in response to cytokine-mediated signals

Functional Variant in Complement C3 Gene Promoter and Genetic Susceptibility to Temporal Lobe Epilepsy and Febrile Seizures

BACKGROUND: Human mesial temporal lobe epilepsies (MTLE) represent the most frequent form of partial epilepsies and are frequently preceded by febrile seizures (FS) in infancy and early childhood. Genetic associations of several complement genes including its central component C3 with disorders of the central nervous system, and the existence of C3 dysregulation in the epilepsies and in the MTLE particularly, make it the C3 gene a good candidate for human MTLE. METHODOLOGY/PRINCIPAL FINDINGS: A case-control association study of the C3 gene was performed in a first series of 122 patients with MTLE and 196 controls. Four haplotypes (HAP1 to 4) comprising GF100472, a newly discovered dinucleotide repeat polymorphism [(CA)8 to (CA)15] in the C3 promoter region showed significant association after Bonferroni correction, in the subgroup of MTLE patients having a personal history of FS (MTLE-FS+). Replication analysis in independent patients and controls confirmed that the rare HAP4 haplotype comprising the minimal length allele of GF100472 [(CA)8], protected against MTLE-FS+. A fifth haplotype (HAP5) with medium-size (CA)11 allele of GF100472 displayed four times higher frequency in controls than in the first cohort of MTLE-FS+ and showed a protective effect against FS through a high statistical significance in an independent population of 97 pure FS. Consistently, (CA)11 allele by its own protected against pure FS in a second group of 148 FS patients. Reporter gene assays showed that GF100472 significantly influenced C3 promoter activity (the higher the number of repeats, the lower the transcriptional activity). Taken together, the consistent genetic data and the functional analysis presented here indicate that a newly-identified and functional polymorphism in the promoter of the complement C3 gene might participate in the genetic susceptibility to human MTLE with a history of FS, and to pure FS. CONCLUSIONS/SIGNIFICANCE: The present study provides important data suggesting for the first time the involvement of the complement system in the genetic susceptibility to epileptic seizures and to epilepsy

Galanin pathogenic mutations in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is a common epilepsy syndrome with a complex etiology. Despite evidence for the participation of genetic factors, the genetic basis of TLE remains largely unknown. A role for the galanin neuropeptide in the regulation of epileptic seizures has been established in animal models more than two decades ago. However, until now there was no report of pathogenic mutations in GAL, the galanin-encoding gene, and therefore its role in human epilepsy was not established. Here, we studied a family with a pair of monozygotic twins affected by TLE and two unaffected siblings born to healthy parents. Exome sequencing revealed that both twins carried a novel de novo mutation (p.A39E) in the GAL gene. Functional analysis revealed that the p.A39E mutant showed antagonistic activity against galanin receptor 1 (GalR1)-mediated response, and decreased binding affinity and reduced agonist properties for GalR2. These findings suggest that the p.A39E mutant could impair galanin signaling in the hippocampus, leading to increased glutamatergic excitation and ultimately to TLE. In a cohort of 582 cases, we did not observe any pathogenic mutations indicating that mutations in GAL are a rare cause of TLE. The identification of a novel de novo mutation in a biologically-relevant candidate gene, coupled with functional evidence that the mutant protein disrupts galanin signaling, strongly supports GAL as the causal gene for the TLE in this family. Given the availability of galanin agonists which inhibit seizures, our findings could potentially have direct implications for the development of anti-epileptic treatment