{"id":17793,"date":"2018-05-03T09:24:34","date_gmt":"2018-05-03T16:24:34","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=17793"},"modified":"2024-01-30T15:14:50","modified_gmt":"2024-01-30T23:14:50","slug":"interconnected-cells-in-a-dish-let-researchers-study-brain-disease","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/de\/news-release\/interconnected-cells-in-a-dish-let-researchers-study-brain-disease\/","title":{"rendered":"Vernetzte Zellen in einer Kulturschale erm\u00f6glichen Forschern die Untersuchung von Gehirnerkrankungen"},"content":{"rendered":"

LA JOLLA\u2014By creating multiple types of neurons from stem cells and observing how they interact, Salk scientists have developed a new way to study the connections between brain cells in the lab. Using the technique, which generates a partial model of the brain, the team showed how communication between neurons is altered in people with schizophrenia. The work appeared in Cell Stem Cell<\/em><\/a> on May 3, 2018.<\/p>\n

\"Salk
Salk researchers used stem cells to derive CA3 pyramidal neurons (green), including a rare subtype of the cells (red). <\/p>\n

Klicken Sie hier<\/a> f\u00fcr ein hochaufl\u00f6sendes Bild.<\/p>\n

Kredit: Salk Institut<\/figcaption><\/figure>\n

\u201cIn a lot of psychiatric diseases, there\u2019s evidence of dysfunction in the connections between cells,\u201d says senior author\u00a0Rusty Gage<\/a>, a professor in Salk\u2019s Laboratory of Genetics. \u201cBut it\u2019s been very difficult to study the functional connections between human neurons in the lab, until now.\u201d<\/p>\n

Previously, researchers wanting to study the underlying molecular mechanism of a disease like schizophrenia would typically focus on one type of brain cell at a time and study whether the levels of genes or proteins were altered in disease cells, or whether signaling pathways seemed to be dysregulated.<\/p>\n

Gage\u2019s team had formerly developed a method for using human stem cells to create dentate gyrus (DG) cells\u2014key neurons in the brain\u2019s hippocampus that have been implicated in a number of psychiatric diseases. In the new work, they adapted that approach to coax stem cells down a different developmental pathway, creating CA3 pyramidal neurons\u2014cells that receive signals from DG neurons in the hippocampus. The resulting CA3 neurons, the team showed, had diverse molecular identities.<\/p>\n

\u201cWe weren\u2019t just getting one type of CA3 neurons,\u201d says Research Associate Anindita Sarkar, the paper\u2019s first and co\u2013corresponding author. \u201cWe were getting a mixture that is a close representation of the mixture we see in a human brain.\u201d Moreover, when the team transplanted the cells into mouse hippocampi, the cells integrated themselves into the networks of neurons already there.<\/p>\n

With that confirmation that the new brain cells were true CA3 neurons, the researchers began mixing them with DG neurons and studying how the cells interacted. Using a method called virus tracing\u2014which relies on the propensity of the rabies virus to follow neuronal connections\u2014they showed that CA3 neurons were forming physical connections both to other CA3 neurons and to DG neurons.<\/p>\n

\"Rusty
Rusty Gage (left) and Anindita Sarkar<\/p>\n

Klicken Sie hier<\/a> for a high-resolution image <\/p>\n

Kredit: Salk Institut<\/figcaption><\/figure>\n

Finally, the team wanted to test out whether they could use these connected neurons to study disease. So they repeated their steps, this time starting with seven different sets of cells\u2014three from people with schizophrenia, and four from healthy controls. They coaxed the cells to revert to their stem cell form, then generated both DG and CA3 neurons. As the neurons matured, the researchers found that there were fewer spikes of activity from the CA3 neurons generated from people with schizophrenia. They got similar findings when they mixed the DG and CA3 neurons\u2014those in the schizophrenic group had dampened activity patterns and less signaling between the sets of neurons.<\/p>\n

\u201cThere\u2019s been evidence that the hippocampus and DG cells are affected by schizophrenia,\u201d says Sarkar. \u201cSo it makes sense that if DG cells are affected, they\u2019re sending fewer signals to CA3 cells.\u201d<\/p>\n

In the future, Gage\u2019s group would like to add additional cell types\u2014such as CA1 neurons\u2014to their model. They\u2019d also like to study how neuronal connections are altered in other diseases.<\/p>\n

\u201cI think this is the next step in disease modeling with stem cells,\u201d says Sarkar. We\u2019ve been doing well looking at individual cells over the last 10 years, but with this whole set of psychiatric diseases\u2014from depression to autism to schizophrenia\u2014we have to look at the connections, as well.\u201d<\/p>\n

Other researchers on the study were Arianna Mei, Apua Paquola, Shani Stern, Cedric Bardy, Jason Klug, Stacy Kim, Neda Neshat, Hyung Joon Kim, Manching Ku, Maxim Shokhirev, David Adamowicz, Maria Marchetto, Roberto Jappelli, Jennifer Erwin, Krishnan Padmanabhan, Matthew Shtrahman and Xin Jin of Salk.<\/p>\n

The work and the researchers involved were supported by grants from CIRM, the Streim Foundation, the Helmsley Foundation, the JPB Foundation, the Engman Foundation, the National Institute of Mental Health, the National Cancer Institute, the Waitt Foundation, and a NARSAD Young Investigator Award.<\/p>","protected":false},"featured_media":17798,"template":"","faculty":[76],"disease-research":[124,167],"class_list":["post-17793","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-rusty-gage","disease-research-neuroscience-and-neurological-disorders","disease-research-schizophrenia"],"acf":[],"yoast_head":"\nInterconnected cells-in-a-dish let researchers study brain disease - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/de\/news-release\/interconnected-cells-in-a-dish-let-researchers-study-brain-disease\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Interconnected cells-in-a-dish let researchers study brain disease - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014By creating multiple types of neurons from stem cells and observing how they interact, Salk scientists have developed a new way to study the connections between brain cells in the lab. 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