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1.
Mol Psychiatry ; 26(7): 2854-2871, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33664475

RESUMEN

Breastmilk contains bioactive molecules essential for brain and cognitive development. While sialylated human milk oligosaccharides (HMOs) have been implicated in phenotypic programming, their selective role and underlying mechanisms remained elusive. Here, we investigated the long-term consequences of a selective lactational deprivation of a specific sialylated HMO in mice. We capitalized on a knock-out (KO) mouse model (B6.129-St6gal1tm2Jxm/J) lacking the gene responsible for the synthesis of sialyl(alpha2,6)lactose (6'SL), one of the two sources of sialic acid (Neu5Ac) to the lactating offspring. Neu5Ac is involved in the formation of brain structures sustaining cognition. To deprive lactating offspring of 6'SL, we cross-fostered newborn wild-type (WT) pups to KO dams, which provide 6'SL-deficient milk. To test whether lactational 6'SL deprivation affects cognitive capabilities in adulthood, we assessed attention, perseveration, and memory. To detail the associated endophenotypes, we investigated hippocampal electrophysiology, plasma metabolomics, and gut microbiota composition. To investigate the underlying molecular mechanisms, we assessed gene expression (at eye-opening and in adulthood) in two brain regions mediating executive functions and memory (hippocampus and prefrontal cortex, PFC). Compared to control mice, WT offspring deprived of 6'SL during lactation exhibited consistent alterations in all cognitive functions addressed, hippocampal electrophysiology, and in pathways regulating the serotonergic system (identified through gut microbiota and plasma metabolomics). These were associated with a site- (PFC) and time-specific (eye-opening) reduced expression of genes involved in central nervous system development. Our data suggest that 6'SL in maternal milk adjusts cognitive development through a short-term upregulation of genes modulating neuronal patterning in the PFC.


Asunto(s)
Lactancia , Leche Humana , Animales , Cognición , Femenino , Lactosa , Ratones , Oligosacáridos
2.
Proc Natl Acad Sci U S A ; 115(30): 7795-7800, 2018 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-29987025

RESUMEN

Brain systems underlying human memory function have been classically investigated studying patients with selective memory impairments. The discovery of rare individuals who have highly superior autobiographical memory (HSAM) provides, instead, an opportunity to investigate the brain systems underlying enhanced memory. Here, we carried out an fMRI investigation of a group of subjects identified as having HSAM. During fMRI scanning, eight subjects with HSAM and 21 control subjects were asked to retrieve autobiographical memories (AMs) as well as non-AMs (e.g., examples of animals). Subjects were instructed to signal the "access" to an AM by a key press and to continue "reliving" it immediately after. Compared with controls, individuals with HSAM provided a richer AM recollection and were faster in accessing AMs. The access to AMs was associated with enhanced prefrontal/hippocampal functional connectivity. AM access also induced increased activity in the left temporoparietal junction and enhanced functional coupling with sensory cortices in subjects with HSAM compared with controls. In contrast, subjects with HSAM did not differ from controls in functional activity during the reliving phase. These findings, based on fMRI assessment, provide evidence of interaction of brain systems engaged in memory retrieval and suggest that enhanced activity of these systems is selectively involved in enabling more efficient access to past experiences in HSAM.


Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Conectoma , Imagen por Resonancia Magnética , Memoria/fisiología , Adulto , Femenino , Humanos , Masculino
3.
Dev Biol ; 411(1): 25-37, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26806704

RESUMEN

HMGA proteins are small nuclear proteins that bind DNA by conserved AT-hook motifs, modify chromatin architecture and assist in gene expression. Two HMGAs (HMGA1 and HMGA2), encoded by distinct genes, exist in mammals and are highly expressed during embryogenesis or reactivated in tumour progression. We here addressed the in vivo role of Xenopus hmga2 in the neural crest cells (NCCs). We show that hmga2 is required for normal NCC specification and development. hmga2 knockdown leads to severe disruption of major skeletal derivatives of anterior NCCs. We show that, within the NCC genetic network, hmga2 acts downstream of msx1, and is required for msx1, pax3 and snail2 activities, thus participating at different levels of the network. Because of hmga2 early effects in NCC specification, the subsequent epithelial-mesenchymal transition (EMT) and migration of NCCs towards the branchial pouches are also compromised. Strictly paralleling results on embryos, interfering with Hmga2 in a breast cancer cell model for EMT leads to molecular effects largely consistent with those observed on NCCs. These data indicate that Hmga2 is recruited in key molecular events that are shared by both NCCs and tumour cells.


Asunto(s)
Diferenciación Celular/genética , Transición Epitelial-Mesenquimal/genética , Proteína HMGA2/fisiología , Cresta Neural/embriología , Proteínas de Xenopus/fisiología , Xenopus laevis/embriología , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Redes Reguladoras de Genes/genética , Proteína HMGA2/genética , Factor de Transcripción MSX1/genética , Neoplasias Mamarias Experimentales/genética , Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/patología , Ratones , Morfolinos/genética , Cresta Neural/citología , Factor de Transcripción PAX3 , Factores de Transcripción Paired Box/genética , Interferencia de ARN , ARN Interferente Pequeño/genética , Factores de Transcripción/genética , Factor de Crecimiento Transformador beta/metabolismo , Proteínas de Xenopus/genética
4.
Dev Genes Evol ; 227(3): 201-211, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28474175

RESUMEN

High mobility group A proteins of vertebrates, HMGA1 and 2, are chromatin architectural factors involved in development, cell differentiation, and neoplastic transformation. Here, we characterize an amphioxus HMGA gene ortholog and analyze its expression. As a basal chordate, amphioxus is well placed to provide insights into the evolution of the HMGA gene family, particularly in the transition from invertebrates to vertebrates. Our phylogenetic analysis supports the basal position of amphioxus, echinoderm, and hemichordate HMGA sequences to those of vertebrate HMGA1 and HMGA2. Consistent with this, the genomic landscape around amphioxus HMGA shares features with both. Whole mount in situ hybridization shows that amphioxus HMGA mRNA is detectable from neurula stage onwards in both nervous and non-nervous tissues. This correlates with protein expression monitored immunocytochemically using antibodies against human HMGA2 protein, revealing especially high levels of expression in cells of the lamellar body, the amphioxus homolog of the pineal, suggesting that the gene may have, among its many functions, an evolutionarily conserved role in photoreceptor differentiation.


Asunto(s)
Proteínas HMGA/genética , Anfioxos/genética , Secuencia de Aminoácidos , Animales , Clonación Molecular , Evolución Molecular , Microscopía Electrónica de Transmisión , Filogenia , Alineación de Secuencia
5.
Front Zool ; 12 Suppl 1: S20, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26816519

RESUMEN

In this article, we refer to an original opinion paper written by Prof. Frank Beach in 1950 ("The Snark was a Boojum"). In his manuscript, Beach explicitly criticised the field of comparative psychology because of the disparity between the original understanding of comparativeness and its practical overly specialised implementation. Specialisation encompassed both experimental species (rats accounted for 70% of all subjects) and test paradigms (dominated by conditioning/learning experiments). Herein, we attempt to evaluate the extent to which these considerations apply to current behavioural neuroscience. Such evaluation is particularly interesting in the context of "translational research" that has recently gained growing attention. As a community, we believe that preclinical findings are intended to inform clinical practice at the level of therapies and knowledge advancements. Yet, limited reproducibility of experimental results and failures to translate preclinical research into clinical trial sindicate that these expectations are not entirely fulfilled. Theoretical considerations suggest that, before concluding that a given phenomenon is of relevance to our species, it should be observed in more than a single experimental model (be it an animal strain or species) and tested in more than a single standardized test battery. Yet, current approaches appear limited in terms of variability and overspecialised in terms of operative procedures. Specifically, as in 1950, rodents (mice instead of rats) still constitute the vast majority of animal species investigated. Additionally, the scientific community strives to homogenise experimental test strategies, thereby not only limiting the generalizability of the findings, but also working against the design of innovative approaches. Finally, we discuss the importance of evolutionary-adaptive considerations within the field of laboratory research. Specifically, resting upon empirical evidence indicating that developing individuals adjust their long-term phenotype according to early environmental demands, we propose that current rearing and housing standards do not adequately prepare experimental subjects to their actual adult environments. Specifically, while the adult life of a laboratory animal is characterized by frequent stimulations and challenges, the neonatal life is dominated by quietness and stability. We suggest that such form of mismatch may remarkably influence the reproducibility and reliability of experimental findings.

6.
Exp Eye Res ; 128: 109-13, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25150087

RESUMEN

Exposure to Stimulating Environments (SE) during development may improve neuroplasticity in central nervous system, protect against neurotoxic damage, and promote neuronal recovery in adult life. While biochemical mechanisms of SE-promoted neuronal plasticity are well known in the brain, much less is known on the signaling cascade governing plasticity and neuroprotection in the retina. In order to investigate if in the retina signaling molecules involved in neuronal plasticity are affected by SE, neonatal CD-1 mice were exposed to moderate corticosterone levels (NC), supplemented through maternal milk during the first postnatal week, or to environmental enrichment (EE) conditions (physical and social stimuli) from early adolescence. Our results showed that both NC and EE increased the phosphorylation level of Extracellularly Regulated Kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB) in the adult retinal tissue. Furthermore, we observed that activated ERK1/2 was restricted to Müller cells, while pCREB was mostly present in the nuclei of retinal neurons. Neither NC, nor EE modified the expression of GFAP, a marker of Müller cells activation. In conclusion our results indicate that both NC and EE activate ERK1/2 and CREB in the retina and provide a biochemical background for the neuroprotective activity exerted by SE against retinal damage. Furthermore, they support the role of Müller glia as a key cell determinant of retinal neuroplasticity.


Asunto(s)
Antiinflamatorios/farmacología , Proteína de Unión a CREB/metabolismo , Corticosterona/farmacología , Exposición a Riesgos Ambientales , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Retina/efectos de los fármacos , Animales , Animales Recién Nacidos , Electroforesis en Gel de Poliacrilamida , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Masculino , Ratones , Plasticidad Neuronal/efectos de los fármacos , Fosforilación , Embarazo , Retina/metabolismo , Neuronas Retinianas
7.
Alcohol Clin Exp Res ; 38(7): 2096-104, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24819037

RESUMEN

BACKGROUND: The complex social behavior exhibited by zebra fish is often leveraged in preclinical studies to investigate whether and how psychoactive compounds modulate inter individual interactions. Due to theoretical and methodological constraints, previous studies on the effects of ethanol (EtOH) on social behavior focused on homogeneous groups in which all individuals were treated, thereby limiting the possibility of isolating all the intervening variables. METHODS: To identify how a social group affects the individual response to EtOH, we quantified the behavior of a single treated individual (acute 0.00, 0.25, 0.50, and 1.00% concentration/volume) swimming together with a group of untreated subjects or alone. A novel in-house-developed automated tracking system was utilized to extract the trajectories of each subject and analyze individual and social behavior. Specifically, we characterized the locomotion of each individual, the cohesion and degree of alignment of the group of untreated subjects, and the interaction between treated and untreated subjects. RESULTS: Individual response to high EtOH concentrations varied depending on the presence or absence of conspecifics. Specifically, EtOH-exposed subjects swam faster when group-tested than in isolation. Remarkably, the presence of the exposed individual substantially influenced the behavior of the untreated subjects. Thus, untreated subjects swam faster when the treated individual was exposed to intermediate EtOH concentrations, without varying their cohesion and degree of alignment. No change in the distance between treated and untreated subjects was found; however, the likelihood that the swimming direction of the treated individual anticipated the response of the group was influenced by EtOH concentration. CONCLUSIONS: Our results demonstrate the feasibility of exposing a single individual to EtOH and test it together with untreated subjects. This approach has the potential to unravel the social determinants of individual response to alcohol, by enabling us to dissociate EtOH exposure from sociality.


Asunto(s)
Conducta Animal/efectos de los fármacos , Etanol/farmacología , Conducta Social , Pez Cebra , Animales , Relación Dosis-Respuesta a Droga , Natación
8.
Psychoneuroendocrinology ; 167: 107102, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38896988

RESUMEN

Type 2 Diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, resulting from deficits in insulin secretion, insulin action, or both. Whilst the role of insulin in the peripheral nervous system has been ascertained in countless studies, its role in the central nervous system (CNS) is emerging only recently. Brain insulin has been lately associated with brain disorders like Alzheimer's disease, obsessive compulsive disorder, and attention deficit hyperactivity disorder. Thus, understanding the role of insulin as a common risk factor for mental and somatic comorbidities may disclose novel preventative and therapeutic approaches. We evaluated general metabolism (glucose tolerance, insulin sensitivity, energy expenditure, lipid metabolism, and polydipsia) and cognitive capabilities (attention, cognitive flexibility, and memory), in adolescent, young adult, and adult male and female TALLYHO/JngJ mice (TH, previously reported to constitute a valid experimental model of T2DM due to impaired insulin signaling). Adult TH mice have also been studied for alterations in gut microbiota diversity and composition. While TH mice exhibited profound deficits in cognitive flexibility and altered glucose metabolism, we observed that these alterations emerged either much earlier (males) or independent of (females) a comprehensive constellation of symptoms, isomorphic to an overt T2DM-like phenotype (insulin resistance, polydipsia, higher energy expenditure, and altered lipid metabolism). We also observed significant sex-dependent alterations in gut microbiota alpha diversity and taxonomy in adult TH mice. Deficits in insulin signaling may represent a common risk factor for both T2DM and CNS-related deficits, which may stem from (partly) independent mechanisms.


Asunto(s)
Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Hiperglucemia , Resistencia a la Insulina , Fenotipo , Animales , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Ratones , Masculino , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Hiperglucemia/metabolismo , Femenino , Resistencia a la Insulina/fisiología , Insulina/metabolismo , Modelos Animales de Enfermedad , Metabolismo Energético/fisiología , Glucemia/metabolismo , Microbioma Gastrointestinal/fisiología , Metabolismo de los Lípidos/fisiología , Polidipsia/metabolismo
9.
Nat Ecol Evol ; 8(3): 536-551, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38200368

RESUMEN

The arrangement and morphology of the vertebrate skull reflect functional and ecological demands, making it a highly adaptable structure. However, the fundamental developmental and macroevolutionary mechanisms leading to different vertebrate skull phenotypes remain unclear. Here we exploit the morphological diversity of squamate reptiles to assess the developmental and evolutionary patterns of skull variation and covariation in the whole head. Our geometric morphometric analysis of a complex squamate ontogenetic dataset (209 specimens, 169 embryos, 44 species), covering stages from craniofacial primordia to fully ossified bones, reveals that morphological differences between snake and lizard skulls arose gradually through changes in spatial relationships (heterotopy) followed by alterations in developmental timing or rate (heterochrony). Along with dynamic spatiotemporal changes in the integration pattern of skull bone shape and topology with surrounding brain tissues and sensory organs, we identify a relatively higher phenotypic integration of the developing snake head compared with lizards. The eye, nasal cavity and Jacobson's organ are pivotal in skull morphogenesis, highlighting the importance of sensory rearrangements in snake evolution. Furthermore, our findings demonstrate the importance of early embryonic, ontogenetic and tissue interactions in shaping craniofacial evolution and ecological diversification in squamates, with implications for the nature of cranio-cerebral relations across vertebrates.


Asunto(s)
Cabeza , Cráneo , Animales , Cráneo/anatomía & histología , Osteogénesis
10.
Sci Adv ; 9(39): eadi6888, 2023 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-37756406

RESUMEN

Snakes represent one-eighth of terrestrial vertebrate diversity, encompassing various lifestyles, ecologies, and morphologies. However, the ecological origins and early evolution of snakes are controversial topics in biology. To address the paucity of well-preserved fossils and the caveats of osteological traits for reconstructing snake evolution, we applied a different ecomorphological hypothesis based on high-definition brain reconstructions of extant Squamata. Our predictive models revealed a burrowing lifestyle with opportunistic behavior at the origin of crown snakes, reflecting a complex ancestral mosaic brain pattern. These findings emphasize the importance of quantitatively tracking the phenotypic diversification of soft tissues-including the accurate definition of intact brain morphological traits such as the cerebellum-in understanding snake evolution and vertebrate paleobiology. Furthermore, our study highlights the power of combining extant and extinct species, soft tissue reconstructions, and osteological traits in tracing the deep evolution of not only snakes but also other groups where fossil data are scarce.


Asunto(s)
Evolución Biológica , Serpientes , Animales , Filogenia , Serpientes/anatomía & histología , Fósiles , Encéfalo
11.
Anat Rec (Hoboken) ; 306(10): 2443-2465, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-36602153

RESUMEN

Vertebrate endocasts are widely used in the fields of paleoneurology and comparative neuroanatomy. The validity of endocranial studies is dependent upon the extent to which an endocast reflects brain morphology. Due to the variable neuroanatomical resolution of vertebrate endocasts, direct information about the brain morphology can be sometimes difficult to assess and needs to be investigated across lineages. Here, we employ X-ray computed tomography (CT), including diffusible iodine-based contrast-enhanced CT, to qualitatively compare brains and endocasts in different species of squamates. The relative position of the squamate brain within the skull, as well as the variability that may exist in such spatial relationships, was examined to help clarify the neurological regions evidence on their endocasts. Our results indicate that squamate endocasts provide variable representation of the brain, depending on species and neuroanatomical regions. The olfactory bulbs and peduncles, cerebral hemispheres, as well as the medulla oblongata represent the most easily discernable brain regions from squamate endocasts. In contrast, the position of the optic lobes, the ventral diencephalon and the pituitary may be difficult to determine depending on species. Finally, squamate endocasts provide very limited or no information about the cerebellum. The spatial relationships revealed here between the brain and the surrounding bones may help to identify each of the endocranial region. However, as one-to-one correspondences between a bone and a specific region appear limited, the exact delimitation of these regions may remain challenging according to species. This study provides a basis for further examination and interpretation of squamate endocast disparity.


Asunto(s)
Encéfalo , Cráneo , Encéfalo/diagnóstico por imagen , Encéfalo/anatomía & histología , Cráneo/diagnóstico por imagen , Cráneo/anatomía & histología , Cabeza/anatomía & histología , Tomografía Computarizada por Rayos X/métodos , Cerebelo , Fósiles , Evolución Biológica
12.
Front Cell Neurosci ; 17: 1091890, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36794260

RESUMEN

Breast milk (BM) is the optimal source of nutrition for mammals' early life. It exerts multiple benefits, including the development of cognitive capabilities and protection against several diseases like obesity and infection of the respiratory tract. However, which components of BM are involved in individual development has remained elusive. Sialylated human milk oligosaccharides (HMOs) may constitute a valid candidate, whereby they represent the principal source of sialic acid and act as building blocks for brain development. We hypothesize that the reduced availability of two HMOs, sialyl(alpha2,6)lactose (6'SL) and sialyl(alpha2,3)lactose (3'SL), may impair attention, cognitive flexibility, and memory in a preclinical model and that the exogenous supplementation of these compounds may contrast the observed deficits. We evaluated cognitive capabilities in a preclinical model exposed to maternal milk containing reduced concentrations of 6'SL and 3'SL during lactation. To modulate their concentrations, we utilized a preclinical model characterized by the absence of genes that synthesize 3'SL and 6'SL (B6.129-St3gal4 tm1.1Jxm and St6gal1tm2Jxm , double genetic deletion), producing milk lacking 3'SL and 6'SL. Then, to ensure exposure to 3'SL-6'SL-poor milk in early life, we adopted a cross-fostering protocol. The outcomes assessed in adulthood were different types of memory, attention and information processing, some of which are part of executive functions. Then, in the second study, we evaluated the long-term compensatory potential of the exogenous oral supplementation of 3'SL and 6'SL during lactation. In the first study, exposure to HMO-poor milk resulted in reduced memory and attention. Specifically, it resulted in impaired working memory in the T-maze test, in reduced spatial memory in the Barnes maze, and in impaired attentional capabilities in the Attentional set-shifting task. In the second part of the study, we did not observe any difference between experimental groups. We hypothesize that the experimental procedures utilized for the exogenous supplementation may have impacted our ability to observe the cognitive read-out in vivo. This study suggests that early life dietary sialylated HMOs play a crucial role in the development of cognitive functions. Future studies are needed to clarify if an exogenous supplementation of these oligosaccharides may compensate for these affected phenotypes.

13.
Anat Rec (Hoboken) ; 306(10): 2425-2442, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-36654187

RESUMEN

Landmark-based geometric morphometrics is widely used to study the morphology of the endocast, or internal mold of the braincase, and the diversity associated with this structure across vertebrates. Landmarks, as the basic unit of such methods, are intended to be points of correspondence, selected depending on the question at hand, whose proper definition is essential to guarantee robustness and reproducibility of results. In this study, 20 landmarks are defined to provide a framework to analyze the morphological variability in squamate endocasts. Ten species representing a cross-section of the diversity of Squamata from both phylogenetic and ecological (i.e., habitat) perspectives were considered, to select landmarks replicable throughout the entire clade, regardless of the degree of neuroanatomical resolution of the endocast. To assess the precision, accuracy, and repeatability of these newly defined landmarks, both intraobserver and interobserver error were investigated. Estimates of measurement error show that most of the landmarks established here are highly replicable, and preliminary results suggest that they capture aspects of endocast shape related to both phylogenetic and ecologic signals. This study provides a basis for further examinations of squamate endocast disparity using landmark-based geometric morphometrics.


Asunto(s)
Lagartos , Cráneo , Animales , Filogenia , Reproducibilidad de los Resultados , Cráneo/anatomía & histología , Serpientes
14.
Sci Rep ; 13(1): 16890, 2023 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-37803045

RESUMEN

Cognitive flexibility involves the capability to switch between different perspectives and implement novel strategies upon changed circumstances. The Wisconsin Card Sorting Test (in humans) and the Attentional Set-Shifting Task (ASST, in rodents) evaluate individual capability to acquire a reward-associated rule and subsequently disregard it in favour of a new one. Both tasks entail consecutive stages wherein subjects discriminate between: two stimuli of a given category (simple discrimination, SD); the stimuli of SD confounded by an irrelevant stimulus of a different category (compound discrimination, CD); different stimuli belonging to the SD category (intradimensional shift, IDS); and two stimuli of the confounding category (extradimensional shift, EDS). The ASST is labour intensive, not sufficiently standardised, and prone to experimental error. Here, we tested the validity of a new, commercially available, automated version of ASST (OPERON) in two independent experiments conducted in: different mouse strains (C57BL/6 and CD1 mice) to confirm their differential cognitive capabilities (Experiment 1); and an experimental model of chronic stress (administration of corticosterone in the drinking water; Experiment 2). In both experiments, OPERON confirmed the findings obtained through the manual version. Just as in Experiment 1 both versions captured the deficit of C57BL/6 mice on the reversal of the CD (CDR), so also in Experiment 2 they provided analogous evidence that corticosterone treated mice have a remarkable impairment in the IDS. Thus, OPERON capitalises upon automated phenotyping to overcome the limitation of the manual version of the ASST while providing comparable results.


Asunto(s)
Corticosterona , Función Ejecutiva , Humanos , Ratones , Animales , Ratones Endogámicos C57BL , Atención , Automatización
15.
Neurosci Biobehav Rev ; 155: 105435, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37913873

RESUMEN

Beside its involvement in somatic dysfunctions, altered insulin signalling constitutes a risk factor for the development of mental disorders like Alzheimer's disease and obsessive-compulsive disorder. While insulin-related somatic and mental disorders are often comorbid, the fundamental mechanisms underlying this association are still elusive. Studies conducted in rodent models appear well suited to help decipher these mechanisms. Specifically, these models are apt to prospective studies in which causative mechanisms can be manipulated via multiple tools (e.g., genetically engineered models and environmental interventions), and experimentally dissociated to control for potential confounding factors. Here, we provide a narrative synthesis of preclinical studies investigating the association between hyperglycaemia - as a proxy of insulin-related metabolic dysfunctions - and impairments in working and spatial memory, and attention. Ultimately, this review will advance our knowledge on the role of glucose metabolism in the comorbidity between somatic and mental illnesses.


Asunto(s)
Enfermedad de Alzheimer , Trastorno Obsesivo Compulsivo , Humanos , Función Ejecutiva , Insulina/metabolismo , Estudios Prospectivos
16.
Neurosci Biobehav Rev ; 150: 105169, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37059405

RESUMEN

Behavioural inflexibility is a symptom of neuropsychiatric and neurodegenerative disorders such as Obsessive-Compulsive Disorder, Autism Spectrum Disorder and Alzheimer's Disease, encompassing the maintenance of a behaviour even when no longer appropriate. Recent evidence suggests that insulin signalling has roles apart from its regulation of peripheral metabolism and mediates behaviourally-relevant central nervous system (CNS) functions including behavioural flexibility. Indeed, insulin resistance is reported to generate anxious, perseverative phenotypes in animal models, with the Type 2 diabetes medication metformin proving to be beneficial for disorders including Alzheimer's Disease. Structural and functional neuroimaging studies of Type 2 diabetes patients have highlighted aberrant connectivity in regions governing salience detection, attention, inhibition and memory. As currently available therapeutic strategies feature high rates of resistance, there is an urgent need to better understand the complex aetiology of behaviour and develop improved therapeutics. In this review, we explore the circuitry underlying behavioural flexibility, changes in Type 2 diabetes, the role of insulin in CNS outcomes and mechanisms of insulin involvement across disorders of behavioural inflexibility.


Asunto(s)
Enfermedad de Alzheimer , Trastorno del Espectro Autista , Diabetes Mellitus Tipo 2 , Trastorno Obsesivo Compulsivo , Animales , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Insulina
17.
Sci Rep ; 12(1): 21976, 2022 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-36539431

RESUMEN

Since humans and robots are increasingly sharing portions of their operational spaces, experimental evidence is needed to ascertain the safety and social acceptability of robots in human-populated environments. Although several studies have aimed at devising strategies for robot trajectory planning to perform safe motion in populated environments, a few efforts have measured to what extent a robot trajectory is accepted by humans. Here, we present a navigation system for autonomous robots that ensures safety and social acceptability of robotic trajectories. We overcome the typical reactive nature of state-of-the-art trajectory planners by leveraging non-cooperative game theory to design a planner that encapsulates human-like features of preservation of a personal space, recognition of groups, sequential and strategized decision making, and smooth obstacle avoidance. Social acceptability is measured through a variation of the Turing test administered in the form of a survey questionnaire to a pool of 691 participants. Comparison terms for our tests are a state-of-the-art navigation algorithm (Enhanced Vector Field Histogram, VFH) and purely human trajectories. While all participants easily recognized the non-human nature of VFH-generated trajectories, the distinction between game-theoretical trajectories and human ones were hardly revealed. Our results mark a strong milestone toward the full integration of robots in social environments.


Asunto(s)
Robótica , Humanos , Algoritmos , Teoría del Juego , Movimiento (Física) , Espacio Personal
18.
Sci Rep ; 12(1): 8185, 2022 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-35581267

RESUMEN

In everyday life, individuals are surrounded by many stimuli that compete to access attention and memory. Evidence shows that perceptually salient stimuli have more chances to capture attention resources, thus to be encoded into short-term memory (STM). However, the impact of perceptual salience on STM at different developmental stages is entirely unexplored. Here we assessed STM performance and meta-memory skills of 6, 10, and 18 years-old participants (total N = 169) using a delayed match-to-sample task. On each trial, participants freely explored a complex (cartoon-like) scene for 4 s. After a retention interval of 4 s, they discriminated the same/different position of a target-object extracted from the area of maximal or minimal salience of the initially-explored scene. Then, they provided a confidence judgment of their STM performance, as an index of meta-memory skills. When taking into account 'confident' responses, we found increased STM performance following targets at maximal versus minimal salience only in adult participants. Similarly, only adults showed enhanced meta-memory capabilities following maximal versus minimal salience targets. These findings documented a late development in the impact of perceptual salience on STM performance and in the improvement of metacognitive capabilities to properly judge the content of one's own memory representation.


Asunto(s)
Memoria a Corto Plazo , Metacognición , Adulto , Atención/fisiología , Humanos , Memoria a Corto Plazo/fisiología
19.
Neuroscience ; 480: 1-8, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34774712

RESUMEN

Individuals with Highly Superior Autobiographical Memory (HSAM) provide the opportunity to investigate the neurobiological substrates of enhanced memory performance. While previous studies started to assess the neural correlates of memory retrieval in HSAM, here we assessed for the first time the intrinsic connectivity of a core memory region, the hippocampus, with the whole brain, in 8 HSAM subjects (HSAMs) and 21 controls during resting-state functional neuroimaging. We found in HSAMs vs. controls disrupted hippocampal resting-state functional connectivity (rsFC) with high-level control regions belonging to the saliency network (the anterior cingulate cortex and the left and right insulae), and to the ventral fronto-parietal attentional network (the temporo-parietal junction and the inferior frontal gyrus), also involved with salience detection. Conversely, HSAMs showed enhanced hippocampal rsFC with sensory regions along the fusiform gyrus and the inferior temporal cortex. This altered pattern of hippocampal rsFC might be interpreted as a reduced capability of HSAMs to discriminate and select salient information, with a subsequent increase in the probability to encode and consolidate sensory information irrespective of their task-relevancy. Ultimately, these findings provide evidence that HSAM might be paradoxically enabled by an altered hippocampal rsFC that bypasses regions involved with salience detection in favor of specialized sensory regions.


Asunto(s)
Memoria Episódica , Encéfalo , Mapeo Encefálico , Hipocampo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética
20.
Brain Sci ; 13(1)2022 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-36672035

RESUMEN

Previous research consistently reported that subjects that were exclusively breastfed (eBF) vs. not-exclusively breastfed (neBF) during infancy (0-6 months) showed increased scores of general intelligence measures (e.g., the intelligence quotient). However, the existent literature largely neglected whether breastfeeding also affects specific cognitive processes, such as attention and working memory (WM) capacity. We tested whether eBF vs. neBF subjects showed performance differences in relation to these two core cognitive functions. The Attention Network Test (ANT), to measure alerting, orienting, and conflict, and the Change Colour Task (CCT), to measure visuospatial WM capacity, were administered to 144 participants divided according to age (6-, 10-, and 18-year-old participants) and breastfeeding (eBF or neBF during 0-6 months of life). Importantly, the sub-groups were homogenous in terms of maternal education, a factor potentially affecting the relation between breastfeeding and cognition. While we found increased performance as a function of participants' age in both tasks, we failed to observe effects related to breastfeeding, as evidenced by Bayesian analyses. These findings highlight for the first time that the pattern of nutrition provided during early infancy does not appear to affect the development of attention and WM capacity, at least starting from the age considered in the present study.

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