A new platform has been developed at the Massachusetts Institute of Technology that allows you to study entire hemispheres of the human brain in 3D observing them with one unprecedented resolution on multiple levelsstarting fromfabric architecture and from cell morphology to then descend into the finer cellular and molecular detailslike the connections between neuronstheir subcellular structures and even the proteins expressed. This sort of zoom has already been experimented with investigate lesions caused by Alzheimer’sas demonstrated by the results of the study published in the journal Science.
L ‘objective last is to create a three-dimensional atlas of human brain cells at subcellular resolution, but not only. “We expect this technology platform to be scalable it will improve our understanding of the functions of human organs and gods disease mechanisms For stimulate the development of new therapies“, say researchers led by Juhyuk Park.
Their work, carried out as part of the Brain Initiative Cell Census Network, led to develop And combine three innovative technologies: MEGAtomea vibrating microtome that slices tissue with an ultra-precise cut without losing connections between cells; mELAST, a hydrogel that makes tissue samples clear, elastic, expandable and reversibly markable, to study them at multiple scales; In the end Unslicea software that reassembles tissue slices to reconstruct the cerebral hemisphere in 3D, even restoring the alignment of individual blood vessels and connections between neurons.
The mix of these technologies allows you to study samples without degrading themOn the contrary: the fabrics become durable and can be analyzed repeatedly, potentially for years.
Observing entire hemispheres of the human brain intact and until the individual connections (synapses) are resolved is doubly important, the researchers point out. First of all allows you to study multiple aspects simultaneously on a single brain, without having to resort to the brains of different people, who can have significant differences, making a comparison difficult. Secondly, scalability and speed of performing this approach (imaging an entire cerebral hemisphere, once prepared, requires 100 hours instead of many months) allow you to create many samples to represent different genders, ages, and disease states, facilitating comparisons to obtain more robust statistics. Study coordinator Kwanghun Chung, a chemical engineer at MIT, already hypothesizes the creation of a bank of fully imaged brains that could be analyzed and relabeled with various markers as needed.
For the moment the platform has been tested on two human brains donated to scienceone healthy and one hit by Alzheimer’s. Without planning too much, the researchers began exploring tissue samples from the orbitofrontal cortex. After identifying regions that had suffered substantial neuronal loss, they decided to delve even deeper using various markers to highlight the relationships between pathogenic factors and different cell types. It thus emerged that synapse loss is concentrated in areas where there is a direct overlap with amyloid plaques.
Video Zoom on a brain affected by Alzheimer’s (source: Chung Lab/MIT Picower Institute)
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