autism spectrum disorders

Counteracting epigenetic mechanisms in autism spectrum disorders

Studying cortical development through the lens of autism spectrum disorders

Reward system function and dysfunction in Autism Spectrum Disorders

New Strategies and Approaches to Tackle and Understand Neurological Disorder

Broadly, the Mauro Costa-Mattioli laboratory (The MCM Lab) encompasses two complementary lines of research. The first one, more traditional but very important, aims at unraveling the molecular mechanisms underlying memory formation (e.g., using state-of-the-art molecular and cell-specific genetic approaches). Learning and memory disorders can strike the brain during development (e.g., Autism Spectrum Disorders and Down Syndrome), as well as during adulthood (e.g., Alzheimer’s disease). We are interested in understanding the specific circuits and molecular pathways that are primarily targeted in these disorders and how they can be restored. To tackle these questions, we use a multidisciplinary, convergent and cross-species approach that combines mouse and fly genetics, molecular biology, electrophysiology, stem cell biology, optogenetics and behavioral techniques. The second line of research, more recent and relatively unexplored, is focused on understanding how gut microbes control CNS driven-behavior and brain function. Our recent discoveries, that microbes in the gut could modulate brain function and behavior in a very powerful way, have added a whole new dimension to the classic view of how complex behaviors are controlled. The unexpected findings have opened new avenues of study for us and are currently driving my lab to answer a host of new and very interesting questions: - What are the gut microbes (and metabolites) that regulate CNS-driven behaviors? Would it be possible to develop an unbiased screening method to identify specific microbes that regulate different behaviors? - If this is the case, can we identify how members of the gut microbiome (and their metabolites) mechanistically influence brain function? - What is the communication channel between the gut microbiota and the brain? Do different gut microbes use different ways to interact with the brain? - Could disruption of the gut microbial ecology cause neurodevelopmental dysfunction? If so, what is the impact of disruption in young and adult animals? - More importantly, could specific restoration of selected bacterial strains (new generation probiotics) represent a novel therapeutic approach for the targeted treatment of neurodevelopmental disorders? - Finally, can we develop microbiota-directed therapeutic foods to repair brain dysfunction in a variety of neurological disorders?

Understanding the cellular and molecular landscape of autism spectrum disorders

Large genomic studies of individuals with autism spectrum disorders (ASD) have revealed approximately 100-200 high risk genes. However, whether these genes function in similar or different signaling networks in brain cells (neurons) remains poorly studied. We are using proteomic technology to build an ASD-associated signaling network map as a resource for the Autism research community. This resource can be used to study Autism risk genes and understand how pathways are convergent, and how patient mutations change the interaction profile. In this presentation, we will present how we developed a pipeline using neurons to build protein-protein interaction profiles. We detected previously unknown interactions between different ASD risk genes that have never been linked together before, and for some genes, we identified new signaling pathways that have not been previously reported. This resource will be available to the research community and will foster collaborations between ASD researchers to help accelerate therapeutics for ASD and related disorders.

Molecular Biology of the Fragile X Syndrome

Silencing of FMR1 and loss of its gene product, FMRP, results in fragile X syndrome (FXS). FMRP binds brain mRNAs and inhibits polypeptide elongation. Using ribosome profiling of the hippocampus, we find that ribosome footprint levels in Fmr1-deficient tissue mostly reflect changes in RNA abundance. Profiling over a time course of ribosome runoff in wild-type tissue reveals a wide range of ribosome translocation rates; on many mRNAs, the ribosomes are stalled. Sucrose gradient ultracentrifugation of hippocampal slices after ribosome runoff reveals that FMRP co-sediments with stalled ribosomes, and its loss results in decline of ribosome stalling on specific mRNAs. One such mRNA encodes SETD2, a lysine methyltransferase that catalyzes H3K36me3. Chromatin immunoprecipitation sequencing (ChIP-seq) demonstrates that loss of FMRP alters the deployment of this histone mark. H3K36me3 is associated with alternative pre-RNA processing, which we find occurs in an FMRP-dependent manner on transcripts linked to neural function and autism spectrum disorders.

Cerebellar inflammation supports autism-related behaviors in the CNTNAP2 mouse model of autism spectrum disorders

Dietary low-level glyphosate and genetic predisposition: a double-hit in autism spectrum disorders?

Hidden targets of autism spectrum disorders: dissecting the pathophysiology of Wac in the ubiquitin-proteasome system

Impaired processing of amplitude-modulated tones in the inferior colliculus in Cacna2d3 mice - a risk gene for autism spectrum disorders in humans

Light sheet imaging of behaviourally activated amygdala neurons in the Fragile-X knockout rat model of autism spectrum disorders

mGlu4 modulation of thalamo-amygdala synaptic transmission and relation to autism spectrum disorders

Mice models and autism spectrum disorders : the example of the Shank3Δ11/Δ 11 mouse

The neuroprotective effect of VEGF-B on the cerebellar destructuration associated with autism spectrum disorders

The physiological correlates of social space in childhood autism spectrum disorders

Striatal dysfunctions with aging in Shank3 KO mouse model of autism spectrum disorders

The anti-reward center in Autism Spectrum Disorders (ASDs)

FENS Forum 2024

GPR50-mediated mitophagy in the pathogenesis of autism spectrum disorders

FENS Forum 2024

Impact of a cocktail of fungicides at the regulatory dose in Europe on the neurodevelopment of a mice model of Autism Spectrum Disorders (ASD)

FENS Forum 2024

Mapping the cell state landscape of autism spectrum disorders

FENS Forum 2024

The social behaviorome in mouse models of autism spectrum disorders (ASD)

FENS Forum 2024

Unraveling gender disparities in autism spectrum disorders: The impact of immunological factors in a mouse model of autism

FENS Forum 2024

Upregulation of Negr1 converges into core impaired processes in autism spectrum disorders

FENS Forum 2024