T-Cell Immune Pathology in the Brain in ASD – M. Anderson MD, Harvard Medical School @Synchrony2020

Описание: Autism is estimated to affect 1 in 59 children in the US and yet, except for rare genetic causes, the etiology in most ASD cases remains unknown.

The presence of increased inflammatory proteins and transcripts in a majority of ASD brain indicates there is an ongoing innate immune response in a large proportion of ASD cases.

We evaluate for adaptive immune cells and damage typical of immune cell mediated cytotoxicity that could potentially drive an innate immune response in the ASD postmortem brain. We found elevated number of lymphocytes in perivascular cuffs that correlates to the quantity of astrocyte-derived round membranous blebs forming from the glia limitans into the perivascular CSF spaces.

Bleb formation is a known cytotoxic reaction to targeted lymphocyte attack and astrocyte blebs are a histologic feature so far unique to ASD. Consistent with an immune cell-mediated injury at perivascular CSF-brain barriers, a subset of white matter vessels had an expanded perivascular space (with jagged contours) and increased perivascular collagen in ASD compared to control brains. Similar T-lymphocyte and astrocyte bleb pathology is observed in subarachnoid and pial surfaces of the cerebral cortex in ASD.

The findings suggest dysregulated cellular immunity may target damage of astrocytes at foci along the glia limitans CSF-brain barrier in many cases of ASD.

Matthew P. Anderson, M.D., Ph.D., is Director of Neuropathology, Beth Israel Deaconess Medical Center; Neuropathologist of Autism BrainNet; and Faculty, Harvard Medical School Ph.D. Program. He won the International Distinguished Dissertation Award (top Ph.D. thesis in science in U.S.A. and Canada, awarded once every 5 years) for seminal work with HHMI Investigator Michael Welsh by uncovering the ion channel and regulatory functions of the cystic fibrosis gene product (Cell, Science, Nature, and PNAS).

At Harvard, his laboratory leverages groundbreaking technologies to investigate the circuit and molecular basis of genetic forms of human neurological and psychiatric disease including epilepsy and autism. His laboratory identified the first human genetic epilepsy disorder with defective postnatal developmental pruning and maturation of glutamatergic circuits (Zhou et al. Nature Medicine 2009). They created the first genetic mouse model of a frequent and strongly penetrant genetic autism spectrum disorder (maternal 15q11-13 triplications; Smith et al. Science TM 2011).

#brain #neuroimmune #immunology #neurology #immunologist #science #braindevelopment

This talk was part of Synchrony 2020 Online Symposium - 'From Bench to Biopharma', organised in partnership with UC Davis MIND Institute and CalTech.

For more Synchrony 2020 talks:    • Synchrony Symposium 2020 - From Bench To B...  


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Synchrony https://synchronysymposium.com/ is the first and only international symposium on translational research in #autism, that brings together academia, #biotech, pharmaceutical companies and #venture partners from around the world with the mission to improve health and quality of life of people with #autismspectrumdisorder

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The BRAIN Foundation https://brainfoundation.org/ is a 501c(3) non-profit. The founders of BRAIN envision a world where every child and adult on the autism spectrum is healthy, participates fully in education and employment, and has a better quality of life. It aims to catalyze research that results in evidence-based interventions for the disabilities associated with autism, and also results in better medical standard of care. To accomplish this, it funds impactful research through #philanthropy and our network of partners in the venture, corporate, and grassroots community.