Biology subjects

Sgado, P.

Publications and source records attributed to Sgado, P..

7 recordsLinked to original sources

bioRxiv2022

Valproic acid exposure alters social visual lateralization and asymmetric gene expression in zebrafish larvae

Cerebral asymmetry is critical for typical brain function and development, at the same time altered brain lateralization seems to be associated with neuropsychiatric disorders. In autism spectrum disorders (ASD) studies have suggested reduced functional and structural cerebral asymmetry, reporting changes in asymmetric activation of brain structures involved in language and social processing, and increased prevalence of left-handedness. Zebrafish are increasingly emerging as model species to study brain lateralization, using asymmetric development of the habenula, a phylogenetically old brain structure associated with social and emotional processing, to investigate the relationship between brain asymmetry and social behavior. We exposed 5-hour post-fertilization zebrafish embryos to valproic acid (VPA), a compound used to model the core signs of ASD in many vertebrate species, and assessed social interaction, visual lateralization and gene expression in the thalamus and the telencephalon. VPA-exposed zebrafish exhibit social deficits and a deconstruction of social visual laterality to the mirror. We also observe changes in the asymmetric expression of the epithalamic marker leftover and in telencephalic gene expression in adult zebrafish. Our data indicate that VPA exposure neutralizes the animals visual field bias, with a complete loss of the left-eye use bias in front of their own mirror image, and alters brain asymmetric gene expression, opening new perspectives to investigate brain lateralization and its link to atypical social cognitive development, considering zebrafish as an animal model for the autistic syndrome.

neuroscience↗

bioRxiv2022

Impaired Epigenesis of Imprinting Predispositions Causes Autism-like Behavioral Phenotypes in Domestic Chicks

Several environmental chemicals are suspected as risk factors for autism spectrum disorder (ASD), including valproic acid (VPA) and pesticides acting on nicotinic acetylcholine receptor (nAChR) if exposed during pregnancy. However, their target processes in fetal neuro-development are unspecified. We report that fetal injection of VPA impaired the imprinting of an artifact object in hatchlings, while the predisposed preference to biological motion (BM) remained intact. Blockade of nAChR acted oppositely, namely, spared imprinting and impaired BM in chicks. Beside ketamine and tubocurarine, significant effects of imidacloprid (a neonicotinoid insecticide) appeared at dose [≤]1ppm. Despite the distinct processes, both VPA and nAChR blockade similarly impaired imprinting of biological image composed of point-light animation. Furthermore, both impairments were rescued by post-natal bumetanide treatment, suggesting common pathology underlying the social attachment malformation. Ambient neonicotinoid could hinder adaptive socialization through impaired development of visual perception in early neonates.

animal behavior and cognition↗

bioRxiv2021

Embryonic valproate exposure alters mesencephalic dopaminergic neurons distribution and septal dopaminergic gene expression in domestic chicks

In recent years, the role of the dopaminergic system in the regulation of social behavior is being progressively outlined, and dysfunctions of the dopaminergic system are increasingly associated with neurodevelopmental disorders, including ASD. To further elucidate the role of the dopaminergic system in ASD, we investigated the effects of embryonic exposure to valproic acid (VPA) on the postnatal development of the mesencephalic DA system in the domestic chick. We found that VPA affected the rostro-caudal distribution of DA neurons, without changing the expression levels of several dopaminergic markers in the mesencephalon. We also investigated a potential consequence of this altered DA neuronal distribution in the septum, a social brain area previously associated to social behaviour in several vertebrate species, describing alterations in the expression of genes linked to DA neurotransmission. These findings support the emerging hypothesis of a role of DA dysfunction in ASD pathogenesis. Together with previous studies showing impairments of early social orienting behaviour, these data also support the use of the domestic chick model to investigate the neurobiological mechanisms involved in early ASD symptoms.

neuroscience↗

bioRxiv2021

Light-induced asymmetries in the embryonic retina are mediated by the vascular system and extracellular matrix

Left-right asymmetries in the nervous system (lateralisation) influence a broad range of behaviours, from social responses to navigation and language. The role and pathways of endogenous and environmental mechanisms in the ontogeny of lateralisation remains to be established. The domestic chick is a model of both endogenous and experience-induced lateralisation driven by light exposure. Following the endogenous rightward rotation of the embryo, the asymmetrical position in the egg results in a greater exposure of the right eye to environmental light. To identify the genetic pathways activated by asymmetric light stimulation, and their time course, we exposed embryos to different light regimes: darkness, 6 hours of light and 24 hours of light. We used RNA-seq to compare gene expression in the right and left retinas and telencephalon. As expected, no differential expression between left and right was present in darkness. We detected differential gene expression in right vs left retina after 6 hours of light exposure. This difference disappeared before 24 hours of light exposure, suggesting that light-induced activation is a self-terminating phenomenon. This transient effect of light exposure was associated with a downregulation of the sensitive-period mediator gene DIO2 (iodothyronine deiodinase 2) in the right retina. No differences between genes expressed in the right vs. left telencephalon were detected. Gene networks associated with lateralisation were connected to vascularisation, cell motility, and the extracellular matrix. Interestingly, we know that the extracellular matrix- including the differentially expressed PDGFRB (platelet-derived growth factor receptor {beta}) gene - is involved in both sensitive periods and in the endogenous chiral mechanism of primary cilia, that drives lateralisation. Our data show a similarity between endogenous and experience-driven lateralisation, identifying functional gene networks that affect lateralisation in a specific time window.

neuroscience↗

bioRxiv2021

Spontaneous visual preference for face-like stimuli is impaired in newly-hatched domestic chicks exposed to valproic acid during embryogenesis

One of the most fascinating properties of the human brain is the capacity of newborn babies to recognize and orient to faces and simple schematic face-like patterns since the first hours of life. A striking feature of these social orienting mechanisms is their transversal appearance in remarkably diverse vertebrate species. Similar to newborn babies, also non-human primates and domestic chicks have been shown to express orienting responses to faces and schematic face-like patterns. More importantly, existing studies have hypothesized that early disturbances of these mechanisms represent one of the earliest biomarkers of social deficits in autism spectrum disorders (ASD). Recent data suggest that newborns at high risk for the disorder express altered responses to schematic face-like configurations. Here we modeled ASD in domestic chicks using the anticonvulsant valproic acid (VPA), and tested the animals for their predisposed preference towards schematic face-like configuration stimuli. We found that VPA impairs the chicks preference responses to the social stimuli. Based on the results shown here and in previous studies, we propose the domestic chicks as elective animal models to study early-emerging neurobehavioural markers and to investigate the biological mechanisms underlying face processing deficits in ASD.

neuroscience↗

bioRxiv2018

Embryonic Exposure to Valproic Acid impairs Social Predispositions for Dynamic Cues of Animate Motion in Newly-Hatched Chicks

Predispositions to preferentially orient towards cues associated with social partners, such as face-like stimuli or biological and animate motion, appear to guide social behavior from the onset of life. These predispositions have been documented in several vertebrate species including human neonates, young monkeys and newly-hatched domestic chicks. Human newborns at high familiar risk of Autism Spectrum Disorder (ASD) show a remarkable deficit in their attention toward these predisposed stimuli, either static and dynamic, compared to newborns at low risk. A previous study showed that prenatal exposure to valproic acid (VPA) (that in humans increases the risk of developing ASD) impairs the chicks predisposition to approach naturalistic social stimuli that convey static configurations of features (a stuffed hen), without impairing general cognitive and learning abilities. Here we investigated the effect of VPA exposure on another class of social predispositions, i.e. the spontaneous preference to approach self-propelled objects, namely objects that display autonomous changes in speed. We observed that the preference for stimuli displaying autonomous changes in speed was impaired in VPA-compared to vehicle-injected chicks. Our results indicate an effect of VPA on the development of predisposed orienting mechanisms towards dynamic stimuli, that could be used to investigate the molecular and neurobiological mechanisms underlying ASD early symptoms.

neuroscience↗

bioRxiv2017

Embryonic Exposure to Valproic Acid Disrupts Social Predispositions in Newly-Hatched Chicks

Biological predispositions to attend to visual cues, such as those associated with face-like stimuli or with biological motion, guide social behavior from the first moments of life and have been documented in human neonates, infant monkeys and newly-hatched domestic chicks. In human neonates at high familial risk of Autism Spectrum Disorder (ASD), a lack of such predispositions has been recently reported. Prompted by these observations, we modeled ASD behavioral deficit in newborn chicks, using embryonic exposure to valproic acid (VPA), the histone deacetylases (HDACs) inhibitor that in humans is associated with an increased risk for developing ASD. We assessed spontaneous predispositions in newly-hatched, visually-naive chicks, by comparing responses to a stuffed hen vs. a scrambled version of it. We found that social predispositions were abolished in VPAtreated chicks. In contrast, experience-dependent learning mechanisms associated with filial imprinting were not affected. Our results indicate a specific effect of VPA on the development of biologically-predisposed social orienting mechanisms, opening new perspectives to investigate the molecular and neurobiological mechanisms involved in early ASD symptoms.

neuroscience↗