Biology subjects

Dardente, H.

Publications and source records attributed to Dardente, H..

5 recordsLinked to original sources

bioRxiv2025

The piggyBac derived transposase 5 (PGBD5) can interact with human piggyBac-like elements

PGBD5 is encoded by a gene domesticated at the chordate origin from a DNA transposon of the piggyBac family. During its evolution, PGBD5s sequence has been under strong purifying selection among vertebrate genomes. This suggests PGBD5 functions in the development and physiology of chordates, as recently demonstrated in mouse and human brain development, where it was implicated in double strand DNA breaks on neurons. However, biochemical PGBD5 activities remain undefined due to lack of appropriate in vitro model systems. Furthermore, coevolution of PGBD5 with hosts has likely reshaped some of its functions, resulting in differences between vertebrate PGBD5 and the insect piggybac transposase (PB). Recent studies have found that PGBD5 can interact with two different "species" of piggyBac-like transposon element (pble). Here, we show that human PGBD5 can interact with four "species" human pbles and to promote their chromosomal integration in cells, a property it shares with insect PB. Human PGBD5 can also bind to distinct chromosomal copies of human pble in cell type-specific manner, and to genomic loci containing inverted repeats in human cells akin to those found in subterminal insect pble ends. These findings expand the scope of potential biological activities of PGBD5 and other domesticated DNA transposases.

genomics↗

bioRxiv2025

The kisspeptin analog C6 reverses reproductive dysfunction in a mouse model of hyperprolactinaemia

Hyperprolactinaemia (HPRL), characterized by elevated prolactin levels, disrupts the hypothalamic-pituitary-gonadal axis, leading to reproductive dysfunctions such as menstrual irregularities, anovulation, and infertility. Current treatments rely on dopamine agonists but are limited by side effects and resistance. Kisspeptin (Kp), a key neuropeptide regulating the reproductive function, offers potential as an alternative therapy. However, Kps short half-life requires impractical administration regimens. To address this, we developed a synthetic Kp analog, C6, with enhanced pharmacokinetics. This study evaluated the effects of C6 compared to Kp in a mouse model of HPRL. Mice received subcutaneous PRL injections for 21 days to induce HPRL, followed by daily or alternate-day intraperitoneal administration of Kp10, C6, or vehicle. Estrous cyclicity, luteinizing hormone (LH) secretion, ovarian histology, and hypothalamic gene expression were analyzed. As expected, the HPRL treatment blocked estrous activity, which was restored by both Kp10, the shortest bioactive isoform of Kp and C6. Histological analysis revealed increased corpora lutea in Kp10- and C6-treated groups, indicating restored ovulation. C6 demonstrated equivalent efficacy to Kp10 in mitigating HPRL-induced reproductive dysfunctions, offering a promising alternative therapy. Future investigations should further explore the mechanistic advantages of C6, particularly its role in LH regulation, to optimize treatment strategies for HPRL-related reproductive disorders.

physiology↗

bioRxiv2025

Affiliative behaviours regulate allostasis development and shape biobehavioural trajectories in horse

Social interactions shape both physiological and behavioural development of offspring and poor care/early caregiver loss are known to promote negative outcomes in adulthood in both animals and humans. How affiliative behaviours impact future development of offspring remains unknown. Here, we used Equus caballus (domestic horse) as a model to investigate this question. By coupling magnetic resonance imaging, longitudinal biobehavioural assessment and advanced multivariate statistical modelling we found that maternal presence during childhood promotes maturation of brain territories involved in both social behaviour (anterior cingulate, retrosplenial cortex) and physiological regulation (hypothalamus, amygdala). Additionally, we found that offsprings benefiting from prolonged maternal presence showed higher default mode network (DMN) connectivity, improved social competences, more efficient feeding behaviours, and metabolic profiles. The present study underscores the salient role of social interactions for the development of allostatic regulation in offspring.

neuroscience↗

bioRxiv2021

Microbiota and stress: a loop that impacts memory

Chronic stress and the gut microbiota appear to comprise a feed-forward loop, which contributes to the development of depressive disorders. Evidence suggests that memory can also be impaired by either chronic stress or microbiota imbalance. However, it remains to be established whether these could be a part of an integrated loop model and be responsible for memory impairments. To shed light on this, we used a two-pronged approach in Japanese quail: first stress-induced alterations in gut microbiota were characterized, then we tested whether this altered microbiota could affect brain and memory function when transferred to a germ-free host. The cecal microbiota of chronically stressed quails was found to be significantly different from that of unstressed individuals with lower and {beta} diversities and increased Bacteroidetes abundance largely represented by the Alistipes genus, a well-known stress target in rodents and humans. The transfer of this altered microbiota into germ-free quails decreased their spatial and cue-based memory abilities as previously demonstrated in the stressed donors. The recipients also displayed increased anxiety-like behavior, reduced basal plasma corticosterone levels and differential gene expression in the brain. Furthermore, cecal microbiota transfer from a chronically stressed individual was sufficient to mimic the adverse impact of chronic stress on memory in recipient hosts and this action may be related to the Alistipes genus. Our results provide evidence of a feed-forward loop system linking the microbiota-gut-brain axis to stress and memory function and suggest that maintaining a healthy microbiota could help alleviate memory impairments linked to chronic stress.

animal behavior and cognition↗

bioRxiv2020

Photoperiodic induction without light-mediated circadian entrainment in a high arctic resident bird

Organisms use changes in photoperiod to anticipate and exploit favourable conditions in a seasonal environment. While species living at temperate latitudes receive day length information as a year-round input, species living in the Arctic may spend as much as two-thirds of the year without experiencing dawn or dusk. This suggests that specialised mechanisms may be required to maintain seasonal synchrony in polar regions.Svalbard ptarmigan (Lagopus muta hyperborea) are resident at 74-81° north latitude. They spend winter in constant darkness (DD) and summer in constant light (LL); extreme photoperiodic conditions under which they do not display overt circadian rhythms.Here we explored how arctic adaptation in circadian biology affects photoperiodic time measurement in captive Svalbard ptarmigan. For this purpose, DD-adapted birds, showing no circadian behaviour, either remained in prolonged DD, were transferred into a simulated natural photoperiod (SNP) or were transferred directly into LL. Birds transferred from DD to LL exhibited a strong photoperiodic response in terms of activation of the hypothalamic thyrotropin-mediated photoperiodic response pathway. This was assayed through expression of the Eya3, Tshβ and deiodinase genes, as well as gonadal development. While transfer to SNP established synchronous diurnal activity patterns, activity in birds transferred from DD to LL showed no evidence of circadian rhythmicity.These data show that the Svalbard ptarmigan does not require circadian entrainment to develop a photoperiodic response involving conserved molecular elements found in temperate species. Further studies are required to define how exactly arctic adaptation modifies seasonal timer mechanisms.Summary statement Svalbard ptarmigan show photoperiodic responses when transferred from constant darkness to constant light without circadian entrainment.Competing Interest StatementThe authors have declared no competing interest.View Full Text

physiology↗