down syndrome

Glial and Neuronal Biology of the Aging Brain Symposium, Alana Down Syndrome Center and Aging Brain Initiative at Picower, MIT

The Aging Brain Initiative (ABI) is an interdisciplinary effort by MIT focusing on understanding neurodegeneration and discovery efforts to find hallmarks of aging, both in health and disease." "The Alana Down Syndrome Center (ADSC) aims to deepen knowledge about Down syndrome and to improve health, autonomy and inclusion of people with this genetic condition." "The ABI and the ADSC have joined forces for this year's symposium to highlight how aging-related changes to the brain overlap with neurological aspects of Down syndrome. Our hope is to encourage greater collaboration between the brain aging and Down syndrome research communities.

Glial and Neuronal Biology of the Aging Brain Symposium, Alana Down Syndrome Center and Aging Brain Initiative at Picower, MIT

The Aging Brain Initiative (ABI) is an interdisciplinary effort by MIT focusing on understanding neurodegeneration and discovery efforts to find hallmarks of aging, both in health and disease." "The Alana Down Syndrome Center (ADSC) aims to deepen knowledge about Down syndrome and to improve health, autonomy and inclusion of people with this genetic condition." "The ABI and the ADSC have joined forces for this year's symposium to highlight how aging-related changes to the brain overlap with neurological aspects of Down syndrome. Our hope is to encourage greater collaboration between the brain aging and Down syndrome research communities.

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?

Treating neurodevelopmental disorders: challenges, issues, problems, concerns, difficulties, harms, worries, doubts, but we need to start from somewhere

Neurodevelopmental disorders are a group of very heterogeneous diseases in which the development of the central nervous system is defective. In neurodevelopmental disorders defective brain development translates into aberrant brain function, which can manifest for example as impaired learning, motor function, or social interaction. Despites years of investigation in animal models and clinical research on neurodevelopmental disorders, there are currently no approved pharmacological treatments for core symptoms of the vast majority of them. Here, I will share some recent work (but also some apprehensions) of our laboratory on the development of strategies for the treatment of neurodevelopmental disorders, with a focus on Down syndrome.

Altered GABA-mediated inhibition during development in neuronal networks from the Ts65Dn mouse model of Down syndrome

Anti-NKCC1 gene therapy rescues cognitive deficits in a mouse model of Down syndrome

Cognitive impairment in Dp(10)2Yey mouse model of Down syndrome is associated with altered neural dynamics and changes in medial prefrontal cortex and hippocampal cellular biology

Comparing the efficacy of selective negative allosteric modulators of α5‐containing GABAA receptors on synaptic inhibition and cognitive deficits in a mouse model of Down syndrome

Convergence of behavioural and molecular phenotypes in mouse and rat models for Down syndrome and consequence for further therapies in human

Dissecting the contribution of astrocytes and upper layer neurons to human cortical circuit dynamics in Down syndrome

Evaluation of a pre/perinatal treatment in a Down Syndrome mouse model

Excessive dendritic inhibition in the prefrontal cortex of a mouse model of Down syndrome persists throughout development into adulthood

Fractional amplitude of low-frequency fluctuation and regional homogeneity in Down Syndrome. A relation with cognitive outcome

Impairment of BACH-1/Nrf-2 axis in Down Syndrome

Investigation of Microglial and Astrocytic Reactivity in Mouse Models of Down Syndrome

N-glycosylation of induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) derived from a person with Down Syndrome (DS) caused by Trisomy 21 (T21)

Selective NKCC1 Inhibitors for the Treatment of Autism, Down syndrome and Brain Disorders with defective NKCC1/KCC2 ratio

Uncovering the signaling pathways to cognitive impairments and neurodegeneration in Down syndrome by cell profiling of the locus coeruleus in trisomic mice

Auditory processing deficits in a rat model of Down syndrome

FENS Forum 2024

Deficit of parvalbumin-positive interneurons and overfunction of somatostatin-positive interneurons are involved in the hippocampus-dependent cognitive impairment of the Ts65Dn mouse model of Down syndrome

FENS Forum 2024

GnRH and miR-200b treatments boost cognition in Down syndrome

FENS Forum 2024

GRIK1 expression at OLM interneurons in the hippocampus and memory deficits in Down syndrome

FENS Forum 2024

Inhibition of long-term potentiation by secretomes of induced pluripotent stem cell-derived Down syndrome neurons: Effect of different anti-tau antibodies

FENS Forum 2024

Microglia contribute to connectivity deficits in Down syndrome by differentially modulating excitatory and inhibitory circuits

FENS Forum 2024

Role of GRIK1 in altered pain sensitivity in a mouse model of Down syndrome

FENS Forum 2024

Role of miR-802 in brain insulin signaling and its impact on Down syndrome

FENS Forum 2024

A single-cell multiomic atlas of human cortical development in Down syndrome identifies candidate mechanisms underlying intellectual disability

FENS Forum 2024

Spatial transcriptomics reveals common pathways in Alzheimer's disease and Down syndrome

FENS Forum 2024