Autism spectrum disorder

Tatsuya Osaki examines vascular contributions to autism spectrum disorder, focusing on blood–brain barrier integrity and cerebral blood-flow dynamics during early development. Rett syndrome provides a starting point: MeCP2 mutations impair endothelial function, suggesting that vascular cells themselves contribute to disease mechanisms. A three-dimensional microphysiological model built from human induced pluripotent stem cells recreates blood–brain barrier structure and function. Patient-derived endothelial cells form perfusable microvascular networks but show impaired barrier function, a find

…We focus on autism spectrum disorder (ASD) models, many cases of which are characterized by stereotypical motor impairments [3]. Specifically, we compare neural activity during a dexterous cued self-feeding task in two trans

Electroencephalography (EEG) has been thoroughly studied for decades in psychiatry research. Yet its integration into clinical practice as a diagnostic/prognostic tool remains unachieved. We hypothesize that a key reason is the underlying patient's heterogeneity, overlooked in psychiatric EEG research relying on a case-control approach. We combine HD-EEG with normative modeling to quantify this heterogeneity using two well-established and extensively investigated EEG characteristics -spectral power and functional connectivity- across a cohort of 1674 patients with attention-deficit/hyperacti

The prefrontal cortex (PFC) is known to be involved in working memory, executive control, attention, and decision making. It integrates internal information and states with external information from the environment which results in timely and appropriate behavioral responses. It remains unknown how distinct excitatory cell types within PFC contribute to population activity and behavior. We investigate two major excitatory cell types within the PFC - extratelencephalic (ET) and intratelencephalic (IT) neurons. Anatomical analysis in transgenic mouse lines shows that ET neurons project to subcor

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition with heterogeneous phenotype. Here, we investigated prefrontal cortex (PFC) alterations and cerebellum-PFC connectivity in the IB2 KO mouse model of ASD. Significant alterations in signal processing and plasticity have been reported in the cerebellar granular layer of IB2 KO mice, confirming the crucial cerebellar involvement in ASD pathophysiology. Given the PFC renowned role in ASD and its functional connections with the cerebellum, we explored the prelimbic cortex (PrL) microcircuitry in IB2 KO and WT mice at differe

The Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition, more prevalent in males, characterized by social behavior impairments. Exposure to valproic acid (VPA) during pregnancy is linked to ASD. In our VPA-mouse model experiment, we examined neuronal activation in the social decision-making network (SDMN) and stress-regulatory nuclei in the brain of juvenile male mice across diverse social settings. VPA treatment effectiveness was validated through a three-chamber sociability test, a standard method for measuring ASD-like behavior. WE used c-Fos immunohistochemistry to c

During embryonic development, neural stem cells, known as radial glial cells (RGCs), give rise to the different subtypes of excitatory neurons and macroglia cells that form the mature neocortex. Precisely regulated mechanisms are crucial for the proper development of this structure, from the generation of neural cells to their correct migration and establishment of specific connections. Among the many genes described to regulate its proper development, cell-cell adhesion molecules such as Cdh2 or its associated protein Afadin play important roles. Inactivation of these genes in the dorsal tele

Sensory anomaly in autism is thought to arise from atypical Bayesian inference processes in the brain. It remains elusive, though, which neuronal circuits are involved. Here we focused on the superior colliculus and performed in vivo two-photon calcium imaging while the mice were engaged in an implicit visual learning task. Following the Bayesian learning principles, wild-type mice showed contextual modulation of the visual responses in the superior colliculus and pupil dynamics, but not in the retinal signals. In contrast, Scn2a-haploinsufficient autism model mice exhibited anomalous modulati

…affects 20-30% of patients with Autism Spectrum Disorder (ASD). Nowadays, the mechanism behind this regressive process is still unknown. To improve our knowledge and find selected target treatments, it is important to establish a model with regressive features. Here, we showed that the Synapsin II Knockout (SynII KO) mouse loses previously acquired social and cognitive abilities in adulthood. Synapsin II is a presynaptic phosphoprotein belonging to the Synapsin family (Syns) involved in neuronal development and in the modulat

Autism spectrum disorder (ASD) is associated with immune alterations and neuroinflammation. Increasing endocannabinoid tone attenuates ASD-related behavioural changes in rodent models and modulates Toll-like receptor (TLR)-induced neuro-immune responses. This study examined the effect of TLR3 activation, in the presence or absence of a fatty acid amide hydrolase (FAAH) inhibitor, on neuroinflammatory gene expression and endocannabinoid levels, in a preclinical rodent model of ASD. Female Sprague-Dawley rats prenatally exposed to either saline or valproic acid (VPA) received 1) the TLR3 agonist

The neural basis of abnormal social behavior in autism spectrum disorder (ASD) remains incompletely understood and previous studies has highlighted that altered myelination could be involved in the pathophysiology of ASD. We have characterized the myelination process during development in the cntnap2-/- mouse model of ASD. We observed that oligodendrocyte differentiation and myelination are transiently impaired during cortical development in cntnap2-/- mice. Thus, we observed a reduction in myelinated fibers, the number of nodes of Ranvier and the proportion of mature oligodendrocytes in somat

Purpose; We wanted to investigate how brain activation patterns of patients with autism spectrum disorder (ASD) differs from that of the neurotypicals (NT) in the context of perspective- taking for pain situations, and how these characteristics are related to the interoceptive accuracy of patients with ASD. Method; We presented the ASD group (N=17) and NT group (N=20) with pain-related visual situations during the fMRI scan, and ordered them 1) to imagine as if the subjects themselves were experiencing those pain situations (Self-perspective), or 2) to imagine as if a third party was experienc

…including motor and neuropsychiatric disorders. They are key modulators of striatal circuit function at both pre- and postsynaptic level, regulating corticostriatal synaptic transmission/plasticity and striatal neuron excitability. We have recently characterized a mouse model of autism spectrum disorder (ASD) obtained by the targeted deletion of the ASD-linked Tshz3 gene in cholinergic neurons (Chat-cKO): these mice show repetitive and restricted behaviors (RRBs) paralleled by a signifi

FoxP genes have been linked to autism spectrum disorder (ASD), a neurodevelopmental disorder that is associated with aberrant connectivity of neural circuits. There is evidence that mutations in FoxP genes lead to impaired cognition, speech, and motor abilities. The goal of our work is to elucidate and characterize distinct molecular mechanisms with which FoxP genes orchestrate neural circuit formation. As a first step, we characterized the temporal and spatial expression pattern of the FoxP transcription factors. To study their impact on neural circuit assembly, we are using the chicken embry

Alterations in social behaviour are one of the core deficits in Autism Spectrum Disorder (ASD). Although it is unclear what the fundamental circuits underlie such deficits, numerous authors have proposed the idea that imbalances in the mesocorticolimbic dopaminergic system could be one of the leading causes. In fact, dopaminergic neurons located in the ventral tegmental area (VTA) that innervate the nucleus accumbens (NAcc) and the prefrontal cortex (PFC) are critical for the creation of reward associations, including social reward. We have previously identified functional dopaminergic alterat

…the risk of neurodevelopmental disorders, including Autism Spectrum Disorder (ASD). Endogenous retroviruses (ERVs) have been proposed as co-factors in the pathogenesis of ASD, also potentially useful as early biomarkers of derailed neurodevelopment. Two preclinical models of ASD, the inbred BTBR T+tf/J (BTBR) mice, and mice prenatally exposed to valproic acid, showed an altered expression of several ERVs and cytokines, in embryos, blood and brain samples at different post-natal ages. The present study aimed to characterize t

Cognitive-motor (C-M) interference is a phenomenon during which demands from concurrent cognitive and motor tasks create competition for available neural resources. Research introduces this competition using dual-task designs to compare performance on single-task situations to dual-tasks, which require both motor and cognitive engagement. However, while some individuals experience C-M interference, others have a more integrative effect, presenting as better adaptation to multi-modal demands. Little is known about how this C-M relationship develops, nor what factors play a role in the integrati

Noradrenaline (NA) is a strong modulator of neuronal activity and many autism spectrum disorder (ASD) symptoms can be attributed to maladaptive activity of locus coeruleus (LC), the main source of forebrain NA. Our lab recently uncovered a role for dysregulated LC-NA function in motor learning delays of the 16p11.2 deletion (+/-) mouse-model of ASD. We found that reduced NA levels in primary motor cortex (M1) caused delays in motor learning and increased neuronal activity in M1 pyramidal neurons. Both behavioral and neuronal phenotypes were rescued by chemogenetic activation of LC-NA. We next

Synaptic dysfunction is a key feature of SHANK-associated disorders such as autism spectrum disorder, schizophrenia, and Phelan-McDermid syndrome. Since detailed knowledge of their effect on synaptic nanostructure remains limited, we investigated such alterations in ex11|SH3 SHANK3-KO mice combining expansion (ExM) and STED microscopy. This enabled high-resolution imaging of mosaic-like arrangements formed by synaptic proteins. We found distinct shape-profiles as fingerprints of the murine postsynaptic scaffold across brain regions and genotypes, as well as alterations in the spatial and molec

Autism spectrum disorder (ASD) is a term used to describe a wide variety of neurodevelopmental disorders that share manifestations and symptoms including intellectual disabilities, social impairments, delayed speech development and repetitive behaviors. Different animal models of ASD share similar electrophysiological and morphological aberrations at the neuronal level. In particular, previous studies have shown that the developmental maturation of GABAergic circuitry appears altered leading to an excitation/inhibition imbalance in the adult. During neurotransmission, the polarity of the GABAe

Epilepsy and autism spectrum disorder have a high degree of comorbidity, likely due to shared underlying predisposing factors. Loss of αV and β3 integrin subunits have been implicated in the onset of epilepsy and autism, respectively. However, the role of the αVβ3 integrin receptor in these disorders remains unclear. Integrins are heterodimeric receptors involved in mechanotransduction between the extracellular matrix and the intracellular cytoskeleton. In the brain, β3 integrin forms heterodimers with αV integrin, regulating the synaptic localization of GluA2-containig AMPA receptors (AMPARs)

Patients with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD), are thought to experience less pain, which is largely based on subjective caregiver or clinician reports of blunted behavioral expression in response to painful stimuli. But recent studies suggest that physiological responses (heart rate, cortisol levels, etc.) to noxious stimuli are heightened compared to neurotypical individuals. The neural valence system is a network of interconnected brain regions that integrates downward sensory stimuli with upward signals reflecting the current physiological state

Fragile X Syndrome (FXS), the most common hereditary cause of intellectual disability and autism spectrum disorder, is caused by the lack of expression of the Fragile X messenger ribonucleoprotein 1 (FMRP). FMRP is a widely expressed RNA-binding protein that plays a pivotal role in regulating protein synthesis. The absence of its expression has been linked to abnormal synaptic transmission and improper dendritic spines morphogenesis, which are tough to underlies the bulk of the cognitive and behavioral defects exhibited by FXS patients. However, our current understanding of FXS physiopathology

…the developmental contribution of many disorder-associated secreted proteins unexplored. A growing body of literature highlights the dysregulation of extracellular fluids in the brain as a common fe